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Expression of neuronal NO synthase α- and β-isoforms in skeletal muscle of mice Biochem. J. (IF 4.1) Pub Date : 2024-05-08 Baum, Oliver
Knowledge of the primary structure of neuronal NO synthase (nNOS) in skeletal muscle is still conflicting and needs further clarification. To elucidate the expression patterns of nNOS isoforms at both mRNA and protein level, systematic reverse transcription (RT)-PCR and epitope mapping by qualitative immunoblot analysis on skeletal muscle of C57/BL6 mice were performed. The ability of the nNOS isoforms
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Biochemical and structural impact of two novel missense mutations in cystathionine β-synthase gene associated with homocystinuria Biochem. J. (IF 4.1) Pub Date : 2024-04-24 Al-Sadeq, Duaa W., Conter, Carolina, Thanassoulas, Angelos, Al-Dewik, Nader, Safieh-Garabedian, Bared, Martínez-Cruz, Luis Alfonso, Nasrallah, Gheyath K., Astegno, Alessandra, Nomikos, Michail
Homocystinuria is a rare disease caused by mutations in the CBS gene that results in a deficiency of cystathionine β-synthase (CBS). CBS is an essential pyridoxal 5′-phosphate (PLP)-dependent enzyme in the transsulfuration pathway, responsible for combining serine with homocysteine to produce cystathionine, whose activity is enhanced by the allosteric regulator S-adenosylmethionine (SAM). CBS also
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AMP-activated protein kinase can be allosterically activated by ADP but AMP remains the key activating ligand Biochem. J. (IF 4.1) Pub Date : 2024-04-24 Hawley, Simon A., Russell, Fiona M., Hardie, D. Grahame
The AMP-activated protein kinase (AMPK) is a sensor of cellular energy status. When activated by increases in ADP:ATP and/or AMP:ATP ratios (signalling energy deficit), AMPK acts to restore energy balance. Binding of AMP to one or more of three CBS repeats (CBS1, CBS3, CBS4) on the AMPK-γ subunit activates the kinase complex by three complementary mechanisms: (i) promoting α-subunit Thr172 phosphorylation
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Activin E is a transforming growth factor β ligand that signals specifically through activin receptor-like kinase 7 Biochem. J. (IF 4.1) Pub Date : 2024-04-10 Vestal, Kylie A., Kattamuri, Chandramohan, Koyiloth, Muhasin, Ongaro, Luisina, Howard, James A., Deaton, Aimee M., Ticau, Simina, Dubey, Aditi, Bernard, Daniel J., Thompson, Thomas B.
Activins are one of the three distinct subclasses within the greater Transforming growth factor β (TGFβ) superfamily. First discovered for their critical roles in reproductive biology, activins have since been shown to alter cellular differentiation and proliferation. At present, members of the activin subclass include activin A (ActA), ActB, ActC, ActE, and the more distant members myostatin and GDF11
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Correction: Proteasome and thiol involvement in quality control of glycosylphosphatidylinositol anchor addition Biochem. J. (IF 4.1) Pub Date : 2024-04-10 Wilbourn, Barry, Nesbeth, Darren N., Wainwright, Linda J., Field, Mark C.
The authors of the original article “Proteasome and thiol involvement in quality control of glycosylphosphatidylinositol anchor addition” DOI: 10.1042/bj3320111: Wilbourn et al., Biochem. J.332, 111–118 (1998) would like to correct Figure 5 of this article. After publication, a reader identified that Figure 5 contained a duplicated Western blot image in panel ‘B’ between the “28” and “29” experimental
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Expression of Concern: Protease-activated receptor-2 promotes kidney tubular epithelial inflammation by inhibiting autophagy via the PI3K/Akt/mTOR signalling pathway Biochem. J. (IF 4.1) Pub Date : 2024-04-10 Du, Chunyang, Zhang, Tao, Xiao, Xia, Shi, Yonghong, Duan, Huijun, Ren, Yunzhuo
The Editorial Office has been made aware of potential issues surrounding the scientific validity of this paper, hence has issued an expression of concern to notify readers whilst the Editorial Office investigates. It has been noted that there seems to be a partial duplication between Figure 4C PAR2-OE control panel and Figure 4E Si-NC MHY1485 panel, as well as a duplication between Figure 7B Sham and
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Long-range electron proton coupling in respiratory complex I — insights from molecular simulations of the quinone chamber and antiporter-like subunits Biochem. J. (IF 4.1) Pub Date : 2024-04-10 Djurabekova, Amina, Lasham, Jonathan, Zdorevskyi, Oleksii, Zickermann, Volker, Sharma, Vivek
Respiratory complex I is a redox-driven proton pump. Several high-resolution structures of complex I have been determined providing important information about the putative proton transfer paths and conformational transitions that may occur during catalysis. However, how redox energy is coupled to the pumping of protons remains unclear. In this article, we review biochemical, structural and molecular
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DoUBLing up: ubiquitin and ubiquitin-like proteases in genome stability Biochem. J. (IF 4.1) Pub Date : 2024-04-10 Foster, Benjamin M., Wang, Zijuan, Schmidt, Christine K.
Maintaining stability of the genome requires dedicated DNA repair and signalling processes that are essential for the faithful duplication and propagation of chromosomes. These DNA damage response (DDR) mechanisms counteract the potentially mutagenic impact of daily genotoxic stresses from both exogenous and endogenous sources. Inherent to these DNA repair pathways is the activity of protein factors
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Evidence that Xrn1 is in complex with Gcn1, and is required for full levels of eIF2α phosphorylation Biochem. J. (IF 4.1) Pub Date : 2024-04-10 Shanmugam, Renuka, Anderson, Reuben, Schiemann, Anja H., Sattlegger, Evelyn
The protein kinase Gcn2 and its effector protein Gcn1 are part of the general amino acid control signalling (GAAC) pathway best known in yeast for its function in maintaining amino acid homeostasis. Under amino acid limitation, Gcn2 becomes activated, subsequently increasing the levels of phosphorylated eIF2α (eIF2α-P). This leads to the increased translation of transcriptional regulators, such as
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The deubiquitinase function of ataxin-3 and its role in the pathogenesis of Machado-Joseph disease and other diseases Biochem. J. (IF 4.1) Pub Date : 2024-03-20 Potapenko, Anastasiya, Davidson, Jennilee M., Lee, Albert, Laird, Angela S.
Machado-Joseph disease (MJD) is a devastating and incurable neurodegenerative disease characterised by progressive ataxia, difficulty speaking and swallowing. Consequently, affected individuals ultimately become wheelchair dependent, require constant care, and face a shortened life expectancy. The monogenic cause of MJD is expansion of a trinucleotide (CAG) repeat region within the ATXN3 gene, which
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Novel modifications of PARP inhibitor veliparib increase PARP1 binding to DNA breaks Biochem. J. (IF 4.1) Pub Date : 2024-03-20 Velagapudi, Uday Kiran, Rouleau-Turcotte, Élise, Billur, Ramya, Shao, Xuwei, Patil, Manisha, Black, Ben E., Pascal, John M., Talele, Tanaji T.
Catalytic poly(ADP-ribose) production by PARP1 is allosterically activated through interaction with DNA breaks, and PARP inhibitor compounds have the potential to influence PARP1 allostery in addition to preventing catalytic activity. Using the benzimidazole-4-carboxamide pharmacophore present in the first generation PARP1 inhibitor veliparib, a series of 11 derivatives was designed, synthesized, and
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Cardiomyocyte-specific deletion of GCN5L1 reduces lysine acetylation and attenuates diastolic dysfunction in aged mice by improving cardiac fatty acid oxidation Biochem. J. (IF 4.1) Pub Date : 2024-03-20 Stewart, Jackson E., Crawford, Jenna M., Mullen, William E., Jacques, Angelica, Stoner, Michael W., Scott, Iain, Thapa, Dharendra
Cardiac mitochondrial dysfunction is a critical contributor to the pathogenesis of aging and many age-related conditions. As such, complete control of mitochondrial function is critical to maintain cardiac efficiency in the aged heart. Lysine acetylation is a reversible post-translational modification shown to regulate several mitochondrial metabolic and biochemical processes. In the present study
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Reporter cell lines to screen for inhibitors or regulators of the KRAS-RAF-MEK1/2-ERK1/2 pathway Biochem. J. (IF 4.1) Pub Date : 2024-03-20 Weatherdon, Laura, Stuart, Kate, Cassidy, Megan, de la Gándara, Alberto Moreno, Okkenhaug, Hanneke, Muellener, Markus, Mckenzie, Grahame, Cook, Simon J., Gilley, Rebecca
The RAS-regulated RAF–MEK1/2–ERK1/2 signalling pathway is activated in cancer due to mutations in RAS proteins (especially KRAS), BRAF, CRAF, MEK1 and MEK2. Whilst inhibitors of KRASG12C (lung adenocarcinoma) and BRAF and MEK1/2 (melanoma and colorectal cancer) are clinically approved, acquired resistance remains a problem. Consequently, the search for new inhibitors (especially of RAS proteins), new
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Mesenteric artery smooth muscle cells from hypertensive rats have increased microtubule acetylation Biochem. J. (IF 4.1) Pub Date : 2024-03-06 Mozzicato, Anthony M., Bastrup, Joakim A., Sanchez-Alonso, Jose L., van der Horst, Jennifer, Gorelik, Julia, Hägglund, Per, Jepps, Thomas A.
The dynamic nature of the microtubule network is dependent in part by post-translational modifications (PTMs) — particularly through acetylation, which stabilizes the microtubule network. Whether PTMs of the microtubule network in vascular smooth muscle cells (VSMCs) contribute to the pathophysiology of hypertension is unknown. The aim of this study was to determine the acetylated state of the microtubule
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Dynamic interactions between SPX proteins, the ubiquitination machinery, and signalling molecules for stress adaptation at a whole-plant level Biochem. J. (IF 4.1) Pub Date : 2024-03-06 Collins, Emma, Shou, Huixia, Mao, Chuanzao, Whelan, James, Jost, Ricarda
The plant macronutrient phosphorus is a scarce resource and plant-available phosphate is limiting in most soil types. Generally, a gene regulatory module called the phosphate starvation response (PSR) enables efficient phosphate acquisition by roots and translocation to other organs. Plants growing on moderate to nutrient-rich soils need to co-ordinate availability of different nutrients and repress
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AMP-activated protein kinase activation suppresses leptin expression independently of adipogenesis in primary murine adipocytes Biochem. J. (IF 4.1) Pub Date : 2024-03-06 Bustraan, Sophia, Bennett, Jane, Whilding, Chad, Pennycook, Betheney R., Smith, David, Barr, Alexis R., Read, Jon, Carling, David, Pollard, Alice
Adipogenesis, defined as the development of mature adipocytes from stem cell precursors, is vital for the expansion, turnover and health of adipose tissue. Loss of adipogenic potential in adipose stem cells, or impairment of adipogenesis is now recognised as an underlying cause of adipose tissue dysfunction and is associated with metabolic disease. In this study, we sought to determine the role of
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Colonic ketogenesis, a microbiota-regulated process, contributes to blood ketones and protects against colitis in mice Biochem. J. (IF 4.1) Pub Date : 2024-02-21 Bass, Kevin, Sivaprakasam, Sathish, Dharmalingam-Nandagopal, Gunadharini, Thangaraju, Muthusamy, Ganapathy, Vadivel
Ketogenesis is considered to occur primarily in liver to generate ketones as an alternative energy source for non-hepatic tissues when glucose availability/utilization is impaired. 3-Hydroxy-3-methylglutaryl-CoA synthase-2 (HMGCS2) mediates the rate-limiting step in this mitochondrial pathway. Publicly available databases show marked down-regulation of HMGCS2 in colonic tissues in Crohn's disease and
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IL-4 activates the futile triacylglyceride cycle for glucose utilization in white adipocytes Biochem. J. (IF 4.1) Pub Date : 2024-02-21 Michurina, Svetlana, Agareva, Margarita, Zubkova, Ekaterina, Menshikov, Mikhail, Stafeev, Iurii, Parfyonova, Yelena
The development of cardiometabolic complications during obesity is strongly associated with chronic latent inflammation in hypertrophied adipose tissue (AT). IL-4 is an anti-inflammatory cytokine, playing a protective role against insulin resistance, glucose intolerance and weight gain. The positive effects of IL-4 are associated not only with the activation of anti-inflammatory immune cells in AT
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The Parkinson's disease related mutant VPS35 (D620N) amplifies the LRRK2 response to endolysosomal stress Biochem. J. (IF 4.1) Pub Date : 2024-02-21 McCarron, Katy R., Elcocks, Hannah, Mortiboys, Heather, Urbé, Sylvie, Clague, Michael J.
The identification of multiple genes linked to Parkinson's disease (PD) invites the question as to how they may co-operate. We have generated isogenic cell lines that inducibly express either wild-type or a mutant form of the retromer component VPS35 (D620N), which has been linked to PD. This has enabled us to test proposed effects of this mutation in a setting where the relative expression reflects
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Abscisic acid triggers vitamin E accumulation by transient transcript activation of VTE5 and VTE6 in sweet cherry fruits Biochem. J. (IF 4.1) Pub Date : 2024-02-21 Muñoz, Paula, Tijero, Verónica, Vincent, Celia, Munné-Bosch, Sergi
Tocopherols are lipophilic antioxidants known as vitamin E and synthesized from the condensation of two metabolic pathways leading to the formation of homogentisate and phytyl diphosphate. While homogentisate is derived from tyrosine metabolism, phytyl diphosphate may be formed from geranylgeranyl diphosphate or phytol recycling from chlorophyll degradation. Here, we hypothesized that abscisic acid
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The role of filamentous matrix molecules in shaping the architecture and emergent properties of bacterial biofilms Biochem. J. (IF 4.1) Pub Date : 2024-02-21 Böhning, Jan, Tarafder, Abul K., Bharat, Tanmay A.M.
Numerous bacteria naturally occur within spatially organised, multicellular communities called biofilms. Moreover, most bacterial infections proceed with biofilm formation, posing major challenges to human health. Within biofilms, bacterial cells are embedded in a primarily self-produced extracellular matrix, which is a defining feature of all biofilms. The biofilm matrix is a complex, viscous mixture
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Beyond the tail: the consequence of context in histone post-translational modification and chromatin research Biochem. J. (IF 4.1) Pub Date : 2024-02-21 Weinzapfel, Ellen N., Fedder-Semmes, Karlie N., Sun, Zu-Wen, Keogh, Michael-Christopher
The role of histone post-translational modifications (PTMs) in chromatin structure and genome function has been the subject of intense debate for more than 60 years. Though complex, the discourse can be summarized in two distinct — and deceptively simple — questions: What is the function of histone PTMs? And how should they be studied? Decades of research show these queries are intricately linked and
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Identification of a 10-mer peptide from the death domain of MyD88 which attenuates inflammation and insulin resistance and improves glucose metabolism Biochem. J. (IF 4.1) Pub Date : 2024-02-21 Ali, Mehmood, Kumari, Tripti, Gupta, Arvind, Akhtar, Sariyah, Verma, Rahul Dev, Ghosh, Jimut Kanti
Insulin resistance (IR) is the key pathophysiological cause of type 2 diabetes, and inflammation has been implicated in it. The death domain (DD) of the adaptor protein, MyD88 plays a crucial role in the transduction of TLR4-associated inflammatory signal. Herein, we have identified a 10-residue peptide (M10), from the DD of MyD88 which seems to be involved in Myddosome formation. We hypothesized that
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Leukotriene B4 receptor 1 does not mediate disease progression in a mouse model of liver fibrosis Biochem. J. (IF 4.1) Pub Date : 2024-02-07 Coyne, Erin S., Nie, Yilin, Abdurrachim, Desiree, Ong, Charlene Zhi Lin, Zhou, Yongqi, Ali, Asad Abu Bakar, Meyers, Stacey, Grein, Jeff, Blumenschein, Wendy, Gongol, Brendan, Liu, Yang, Hugelshofer, Cedric, Carballo-Jane, Ester, Talukdar, Saswata
Metabolic dysfunction-associated steatohepatitis (MASH) is a prevalent liver disease that can progress to fibrosis, cirrhosis, hepatocellular carcinoma, and ultimately death, but there are no approved therapies. Leukotriene B4 (LTB4) is a potent pro-inflammatory chemoattractant that drives macrophage and neutrophil chemotaxis, and genetic loss or inhibition of its high-affinity receptor, leukotriene
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The consequence of ATP synthase dimer angle on mitochondrial morphology studied by cryo-electron tomography Biochem. J. (IF 4.1) Pub Date : 2024-02-07 Buzzard, Emma, McLaren, Mathew, Bragoszewski, Piotr, Brancaccio, Andrea, Ford, Holly C., Daum, Bertram, Kuwabara, Patricia, Collinson, Ian, Gold, Vicki A.M.
Mitochondrial ATP synthases form rows of dimers, which induce membrane curvature to give cristae their characteristic lamellar or tubular morphology. The angle formed between the central stalks of ATP synthase dimers varies between species. Using cryo-electron tomography and sub-tomogram averaging, we determined the structure of the ATP synthase dimer from the nematode worm Caenorhabditis elegans and
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The role of mitochondrial RNA association for mitochondrial homeostasis in neurons Biochem. J. (IF 4.1) Pub Date : 2024-02-07 Segura, Inmaculada, Harbauer, Angelika
The sub-compartmentalization of cellular processes is especially important in highly polarized cells such as neurons, as their function rely on their complex morphology. The association of RNAs to the mitochondrial surface is a conserved feature from yeast to humans and it regulates several aspects of mitochondrial physiology and, hence, cellular functions. In neurons, mitochondria are emerging as
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Proximity labelling reveals effects of disease-causing mutation on the DNAJC5/cysteine string protein α interactome Biochem. J. (IF 4.1) Pub Date : 2024-02-07 Barker, Eleanor, Milburn, Amy E., Helassa, Nordine, Hammond, Dean E., Sanchez-Soriano, Natalia, Morgan, Alan, Barclay, Jeff W.
Cysteine string protein α (CSPα), also known as DNAJC5, is a member of the DnaJ/Hsp40 family of co-chaperones. The name derives from a cysteine-rich domain, palmitoylation of which enables localisation to intracellular membranes, notably neuronal synaptic vesicles. Mutations in the DNAJC5 gene that encodes CSPα cause autosomal dominant, adult-onset neuronal ceroid lipofuscinosis (ANCL), a rare neurodegenerative
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The mTORC2 signaling network: targets and cross-talks Biochem. J. (IF 4.1) Pub Date : 2024-01-25 Ragupathi, Aparna, Kim, Christian, Jacinto, Estela
The mechanistic target of rapamycin, mTOR, controls cell metabolism in response to growth signals and stress stimuli. The cellular functions of mTOR are mediated by two distinct protein complexes, mTOR complex 1 (mTORC1) and mTORC2. Rapamycin and its analogs are currently used in the clinic to treat a variety of diseases and have been instrumental in delineating the functions of its direct target,
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A highly conserved ligand-binding site for AccA transporters of antibiotic and quorum-sensing regulator in Agrobacterium leads to a different specificity Biochem. J. (IF 4.1) Pub Date : 2024-01-25 Moréra, Solange, Vigouroux, Armelle, Aumont-Nicaise, Magali, Ahmar, Mohammed, Meyer, Thibault, El Sahili, Abbas, Deicsics, Grégory, González-Mula, Almudena, Li, Sizhe, Doré, Jeanne, Sirigu, Serena, Legrand, Pierre, Penot, Camille, André, François, Faure, Denis, Soulère, Laurent, Queneau, Yves, Vial, Ludovic
Plants genetically modified by the pathogenic Agrobacterium strain C58 synthesize agrocinopines A and B, whereas those modified by the pathogenic strain Bo542 produce agrocinopines C and D. The four agrocinopines (A, B, C and D) serve as nutrients by agrobacteria and signaling molecule for the dissemination of virulence genes. They share the uncommon pyranose-2-phosphate motif, represented by the l-arabinopyranose
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Pseudouridylation-mediated gene expression modulation Biochem. J. (IF 4.1) Pub Date : 2024-01-10 Chen, Jonathan L., Leeder, W.-Matthias, Morais, Pedro, Adachi, Hironori, Yu, Yi-Tao
RNA-guided pseudouridylation, a widespread post-transcriptional RNA modification, has recently gained recognition for its role in cellular processes such as pre-mRNA splicing and the modulation of premature termination codon (PTC) readthrough. This review provides insights into its mechanisms, functions, and potential therapeutic applications. It examines the mechanisms governing RNA-guided pseudouridylation
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The role of phosphorylation in calmodulin-mediated gating of human AQP0 Biochem. J. (IF 4.1) Pub Date : 2024-01-10 Kreida, Stefan, Roche, Jennifer Virginia, Missel, Julie Winkel, Al-Jubair, Tamim, Hagströmer, Carl Johan, Wittenbecher, Veronika, Linse, Sara, Gourdon, Pontus, Törnroth-Horsefield, Susanna
Aquaporin-0 (AQP0) is the main water channel in the mammalian lens and is involved in accommodation and maintaining lens transparency. AQP0 binds the Ca2+-sensing protein calmodulin (CaM) and this interaction is believed to gate its water permeability by closing the water-conducting pore. Here, we express recombinant and functional human AQP0 in Pichia pastoris and investigate how phosphorylation affects
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Non-cross-linking advanced glycation end products affect prohormone processing Biochem. J. (IF 4.1) Pub Date : 2024-01-10 Brings, Sebastian, Mier, Walter, Beijer, Barbro, Kliemank, Elisabeth, Herzig, Stephan, Szendroedi, Julia, Nawroth, Peter P., Fleming, Thomas
Advanced glycation end products (AGEs) are non-enzymatic post-translational modifications of amino acids and are associated with diabetic complications. One proposed pathomechanism is the impaired processing of AGE-modified proteins or peptides including prohormones. Two approaches were applied to investigate whether substrate modification with AGEs affects the processing of substrates like prohormones
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MicroRNA, miR-501 regulate the V(D)J recombination in B cells Biochem. J. (IF 4.1) Pub Date : 2023-12-20 Kumari, Rupa, Roy, Urbi, Desai, Sagar, Mondal, Arannya S., Nair, Rajshree R., Nilavar, Namrata, Choudhary, Bibha, Raghavan, Sathees C.
The stringent regulation of RAGs (Recombination activating genes), the site-specific endonuclease responsible for V(D)J recombination, is important to prevent genomic rearrangements and chromosomal translocations in lymphoid cells. In the present study, we identify a microRNA, miR-501, which can regulate the expression of RAG1 in lymphoid cells. Overexpression of the pre-miRNA construct led to the
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Up-regulation of SLC7A11/xCT creates a vulnerability to selenocystine-induced cytotoxicity Biochem. J. (IF 4.1) Pub Date : 2023-12-20 Tan, Shawn Lu Wen, Tan, Hui Min, Israeli, Erez, Fatihah, Indah, Ramachandran, Vignesh, Ali, Shamsia Bte, Goh, Shane Jun An, Wee, Jillian, Tan, Alicia Qian Ler, Tam, Wai Leong, Han, Weiping
The SLC7A11/xCT cystine and glutamate antiporter has emerged as an attractive target for cancer therapy due to its selective overexpression in multiple cancers and its role in preventing ferroptosis. Utilizing pharmacological and genetic approaches in hepatocellular carcinoma cell lines, we demonstrate that overexpression of SLC7A11 engenders hypersensitivity towards l-selenocystine, a naturally occurring
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Correction: Mechanism of sphingosine 1-phosphate clearance from blood Biochem. J. (IF 4.1) Pub Date : 2023-12-20 Kharel, Yugesh, Huang, Tao, Salamon, Anita, Harris, Thurl E., Santos, Webster L., Lynch, Kevin R.
The authors of the original article would like to correct their paper. The authors have been made aware of an error regarding Figure 3. The third panel was missing from this figure. The authors would like to apologise to readers for this error which does not affect the overall conclusion of the article. The corrected Figure 3 and Figure 3 caption are provided.Kharel, Y., Huang, T., Salamon, A., Harris
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Sperm induce a secondary increase in ATP levels in mouse eggs that is independent of Ca2+ oscillations Biochem. J. (IF 4.1) Pub Date : 2023-12-20 Ikie-Eshalomi, Cindy, Aliyev, Elnur, Hoehn, Sven, Jurkowski, Tomasz P., Swann, Karl
Egg activation at fertilization in mouse eggs is caused by a series of cytosolic Ca2+ oscillations that are associated with an increase in ATP concentrations driven by increased mitochondrial activity. We have investigated the role of Ca2+ oscillations in these changes in ATP at fertilization by measuring the dynamics of ATP and Ca2+ in mouse eggs. An initial ATP increase started with the first Ca2+
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Into the fold: advances in understanding aPKC membrane dynamics Biochem. J. (IF 4.1) Pub Date : 2023-12-20 Cobbaut, Mathias, Parker, Peter J., McDonald, Neil Q.
Atypical protein kinase Cs (aPKCs) are part of the PKC family of protein kinases and are atypical because they don't respond to the canonical PKC activators diacylglycerol (DAG) and Ca2+. They are central to the organization of polarized cells and are deregulated in several cancers. aPKC recruitment to the plasma membrane compartment is crucial to their encounter with substrates associated with polarizing
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Lysine methylation signaling in skeletal muscle biology: from myogenesis to clinical insights Biochem. J. (IF 4.1) Pub Date : 2023-12-13 Cordeiro-Spinetti, Eric, Rothbart, Scott B.
Lysine methylation signaling is well studied for its key roles in the regulation of transcription states through modifications on histone proteins. While histone lysine methylation has been extensively studied, recent discoveries of lysine methylation on thousands of non-histone proteins has broadened our appreciation for this small chemical modification in the regulation of protein function. In this
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Engineering of CYP82Y1, a cytochrome P450 monooxygenase: a key enzyme in noscapine biosynthesis in opium poppy Biochem. J. (IF 4.1) Pub Date : 2023-12-13 Aghaali, Zahra, Naghavi, Mohammad Reza
Protein engineering provides a powerful base for the circumvention of challenges tied with characteristics accountable for enzyme functions. CYP82Y1 introduces a hydroxyl group (−OH) into C1 of N-methylcanadine as the substrate to yield 1-hydroxy-N-methylcanadine. This chemical process has been found to be the gateway to noscapine biosynthesis. Owning to the importance of CYP82Y1 in this biosynthetic
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Understanding interleukin 11 as a disease gene and therapeutic target Biochem. J. (IF 4.1) Pub Date : 2023-12-13 Cook, Stuart A.
Interleukin 11 (IL11) is an elusive member of the IL6 family of cytokines. While initially thought to be a haematopoietic and cytoprotective factor, more recent data show instead that IL11 is redundant for haematopoiesis and toxic. In this review, the reasons that led to the original misunderstandings of IL11 biology, which are now understandable, are explained with particular attention on the use
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Frequent loss-of-function mutations in the AMPK-α2 catalytic subunit suggest a tumour suppressor role in human skin cancers Biochem. J. (IF 4.1) Pub Date : 2023-12-13 Ross, Fiona A., Hawley, Simon A., Russell, Fiona M., Goodman, Nicola, Hardie, D. Grahame
The AMP-activated protein kinase (AMPK) is a sensor of cellular energy status activated by increases in AMP or ADP relative to ATP. Once activated, it phosphorylates targets that promote ATP-generating catabolic pathways or inhibit ATP-consuming anabolic pathways, helping to restore cellular energy balance. Analysis of human cancer genome studies reveals that the PRKAA2 gene (encoding the α2 isoform
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A guide to ERK dynamics, part 1: mechanisms and models Biochem. J. (IF 4.1) Pub Date : 2023-12-13 Ram, Abhineet, Murphy, Devan, DeCuzzi, Nicholaus, Patankar, Madhura, Hu, Jason, Pargett, Michael, Albeck, John G.
Extracellular signal-regulated kinase (ERK) has long been studied as a key driver of both essential cellular processes and disease. A persistent question has been how this single pathway is able to direct multiple cell behaviors, including growth, proliferation, and death. Modern biosensor studies have revealed that the temporal pattern of ERK activity is highly variable and heterogeneous, and critically
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A guide to ERK dynamics, part 2: downstream decoding Biochem. J. (IF 4.1) Pub Date : 2023-12-13 Ram, Abhineet, Murphy, Devan, DeCuzzi, Nicholaus, Patankar, Madhura, Hu, Jason, Pargett, Michael, Albeck, John G.
Signaling by the extracellular signal-regulated kinase (ERK) pathway controls many cellular processes, including cell division, death, and differentiation. In this second installment of a two-part review, we address the question of how the ERK pathway exerts distinct and context-specific effects on multiple processes. We discuss how the dynamics of ERK activity induce selective changes in gene expression
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Skin in the game: pannexin channels in healthy and cancerous skin Biochem. J. (IF 4.1) Pub Date : 2023-12-13 O'Donnell, Brooke L., Penuela, Silvia
The skin is a highly organized tissue composed of multiple layers and cell types that require coordinated cell to cell communication to maintain tissue homeostasis. In skin cancer, this organized structure and communication is disrupted, prompting the malignant transformation of healthy cells into melanoma, basal cell carcinoma or squamous cell carcinoma tumours. One such family of channel proteins
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Elucidating the interaction of C-terminal domain of Vaccinia-Related Kinase 2A (VRK2A) with B-cell lymphoma-extra Large (Bcl-xL) to decipher its anti-apoptotic role in cancer Biochem. J. (IF 4.1) Pub Date : 2023-11-29 Puja, Rashmi, Dutta, Shubhankar, Bose, Kakoli
Vaccinia-Related Kinase 2 (VRK2) is an anti-apoptotic Ser/Thr kinase that enhances drug sensitivity in cancer cells. This protein exists in two isoforms: VRK2A, the longer variant, and VRK2B, which lacks the C-terminal region and transmembrane domain. While the therapeutic importance of VRK2 family proteins is known, the specific roles of VRK2A and its interplay with apoptotic regulator Bcl-xL (B-cell
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PHF1 compartmentalizes PRC2 via phase separation Biochem. J. (IF 4.1) Pub Date : 2023-11-29 Lu, Genzhe, Li, Pilong
Polycomb repressive complex 2 (PRC2) is central to polycomb repression as it trimethylates lysine 27 on histone H3 (H3K27me3). How PRC2 is recruited to its targets to deposit H3K27me3 remains an open question. Polycomb-like (PCL) proteins, a group of conserved PRC2 accessory proteins, can direct PRC2 to its targets. In this report, we demonstrate that a PCL protein named PHF1 forms phase-separated
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Plant adaptation to climate change Biochem. J. (IF 4.1) Pub Date : 2023-11-29 Foyer, Christine H., Kranner, Ilse
Plants are vital to human health and well-being, as well as helping to protect the environment against the negative impacts of climate change. They are an essential part of the ‘One Health’ strategy that seeks to balance and optimize the health of people, animals and the environment. Crucially, plants are central to nature-based solutions to climate mitigation, not least because soil carbon storage
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Enzyme function and evolution through the lens of bioinformatics Biochem. J. (IF 4.1) Pub Date : 2023-11-29 Ribeiro, Antonio J. M., Riziotis, Ioannis G., Borkakoti, Neera, Thornton, Janet M.
Enzymes have been shaped by evolution over billions of years to catalyse the chemical reactions that support life on earth. Dispersed in the literature, or organised in online databases, knowledge about enzymes can be structured in distinct dimensions, either related to their quality as biological macromolecules, such as their sequence and structure, or related to their chemical functions, such as
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Loss of the methylarginine reader function of SND1 confers resistance to hepatocellular carcinoma Biochem. J. (IF 4.1) Pub Date : 2023-11-29 Wright, Tanner, Wang, Yalong, Stratton, Sabrina A., Sebastian, Manu, Liu, Bin, Johnson, David G., Bedford, Mark T.
Staphylococcal nuclease Tudor domain containing 1 (SND1) protein is an oncogene that ‘reads’ methylarginine marks through its Tudor domain. Specifically, it recognizes methylation marks deposited by protein arginine methyltransferase 5 (PRMT5), which is also known to promote tumorigenesis. Although SND1 can drive hepatocellular carcinoma (HCC), it is unclear whether the SND1 Tudor domain is needed
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Catalysis of non-canonical protein ubiquitylation by the ARIH1 ubiquitin ligase Biochem. J. (IF 4.1) Pub Date : 2023-11-29 Purser, Nicholas, Tripathi-Giesgen, Ishita, Li, Jerry, Scott, Daniel C., Horn-Ghetko, Daniel, Baek, Kheewoong, Schulman, Brenda A., Alpi, Arno F., Kleiger, Gary
Protein ubiquitylation typically involves isopeptide bond formation between the C-terminus of ubiquitin to the side-chain amino group on Lys residues. However, several ubiquitin ligases (E3s) have recently been identified that ubiquitylate proteins on non-Lys residues. For instance, HOIL-1 belongs to the RING-in-between RING (RBR) class of E3s and has an established role in Ser ubiquitylation. Given
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Elevated atmospheric carbon dioxide and plant immunity to fungal pathogens: do the risks outweigh the benefits? Biochem. J. (IF 4.1) Pub Date : 2023-11-29 Smith, Freya, Luna, Estrella
Anthropogenic emissions have caused atmospheric carbon dioxide (CO2) concentrations to double since the industrial revolution. Although this could benefit plant growth from the ‘CO2 fertilisation’ effect, recent studies report conflicting impacts of elevated CO2 (eCO2) on plant–pathogen interactions. Fungal pathogens are the leading cause of plant disease. Since climate change has been shown to affect
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Interactions of mitochondrial and skeletal muscle biology in mitochondrial myopathy Biochem. J. (IF 4.1) Pub Date : 2023-11-15 Di Leo, Valeria, Bernardino Gomes, Tiago M., Vincent, Amy E.
Mitochondrial dysfunction in skeletal muscle fibres occurs with both healthy aging and a range of neuromuscular diseases. The impact of mitochondrial dysfunction in skeletal muscle and the way muscle fibres adapt to this dysfunction is important to understand disease mechanisms and to develop therapeutic interventions. Furthermore, interactions between mitochondrial dysfunction and skeletal muscle
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Biochemical investigations of polyphenol degradation enzymes in the phototrophic bacterium Rubrivivax gelatinosus Biochem. J. (IF 4.1) Pub Date : 2023-11-15 Cui, Mengyu, Wei, Yifeng, Tan, Jason, Li, Tong, Jiao, Xinan, Zhou, Yan
Phloroglucinol (1,3,5-trihydroxybenzene) is an important intermediate in the degradation of flavonoids and tannins by anaerobic bacteria. Recent studies have shed light on the enzymatic mechanism of phloroglucinol degradation in butyrate-forming anaerobic bacteria, including environmental and intestinal bacteria such as Clostridium and Flavonifractor sp. Phloroglucinol degradation gene clusters have
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Activating mutations drive human MEK1 kinase using a gear-shifting mechanism Biochem. J. (IF 4.1) Pub Date : 2023-11-15 Patil, Keshav, Wang, Yiming, Chen, Zhangtao, Suresh, Krishna, Radhakrishnan, Ravi
There is an unmet need to classify cancer-promoting kinase mutations in a mechanistically cognizant way. The challenge is to understand how mutations stabilize different kinase configurations to alter function, and how this influences pathogenic potential of the kinase and its responses to therapeutic inhibitors. This goal is made more challenging by the complexity of the mutational landscape of diseases
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Targeting bacterial degradation machinery as an antibacterial strategy Biochem. J. (IF 4.1) Pub Date : 2023-11-15 Petkov, Radoslav, Camp, Amy H., Isaacson, Rivka L., Torpey, James H.
The exploitation of a cell's natural degradation machinery for therapeutic purposes is an exciting research area in its infancy with respect to bacteria. Here, we review current strategies targeting the ClpCP system, which is a proteolytic degradation complex essential in the biology of many bacterial species of scientific interest. Strategies include using natural product antibiotics or acyldepsipeptides
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Fluorescent biosensors illuminate the spatial regulation of cell signaling across scales Biochem. J. (IF 4.1) Pub Date : 2023-10-31 Lyons, Anne C., Mehta, Sohum, Zhang, Jin
As cell signaling research has advanced, it has become clearer that signal transduction has complex spatiotemporal regulation that goes beyond foundational linear transduction models. Several technologies have enabled these discoveries, including fluorescent biosensors designed to report live biochemical signaling events. As genetically encoded and live-cell compatible tools, fluorescent biosensors
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Microrchidia 2/histone deacetylase 1 complex regulates E-cadherin gene expression and function Biochem. J. (IF 4.1) Pub Date : 2023-10-31 Thomas, Liz, Chutani, Namita, R, Krishna, Nair, Asha S., Yellapu, Nanda Kumar, Karyala, Prashanthi, Pakala, Suresh B.
Although Microrchidia 2 (MORC2) is widely overexpressed in human malignancies and linked to cancer cell proliferation, metabolism, and metastasis, the mechanism of action of MORC2 in cancer cell migration and invasion is yet undeciphered. Here, we identified for the first time that MORC2, a chromatin remodeler, regulates E-cadherin expression and, subsequently regulates breast cancer cell migration
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UBE2A/B is the trans-acting factor mediating mechanotransduction and contact inhibition Biochem. J. (IF 4.1) Pub Date : 2023-10-31 Feng, Mingwei, Wang, Jiale, Li, Kangjing, Nakamura, Fumihiko
Mechanotransduction and contact inhibition (CI) control gene expression to regulate proliferation, differentiation, and even tumorigenesis of cells. However, their downstream trans-acting factors (TAFs) are not well known due to a lack of a high-throughput method to quantitatively detect them. Here, we developed a method to identify TAFs on the cis-acting sequences that reside in open chromatin or
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Mitophagy in yeast: known unknowns and unknown unknowns Biochem. J. (IF 4.1) Pub Date : 2023-10-31 Abeliovich, Hagai
Mitophagy, the autophagic breakdown of mitochondria, is observed in eukaryotic cells under various different physiological circumstances. These can be broadly categorized into two types: mitophagy related to quality control events and mitophagy induced during developmental transitions. Quality control mitophagy involves the lysosomal or vacuolar degradation of malfunctioning or superfluous mitochondria
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Revisiting the roles of cAMP signalling in the progression of prostate cancer Biochem. J. (IF 4.1) Pub Date : 2023-10-31 Parsons, Emma C., Hoffmann, Ralf, Baillie, George S.
Prostate cancer is one of the most common cancers in men and one of the top causes of death in men worldwide. Development and function of both normal prostate cells and early-stage prostate cancer cells are dependent on the cross-talk between androgen signalling systems and a variety of other transduction pathways which drive differentiation of these cells towards castration-resistance. One such signalling