TRIM proteins are characterized by their conserved N-terminal RING, B-box, and coiled-coil domains. These proteins are efficient regulators of autophagy, apoptosis, and innate immune responses and confer immunity against viruses and bacteria. TRIMs function as receptors or scaffold proteins that target substrates for autophagy-mediated degradation. Most TRIMs interact with the BECN1-ULK1 complex to form TRIMosomes, thereby efficiently targeting substrates to autophagosomes. They regulate the functions of ATG proteins through physical interactions or ubiquitination. TRIMs affect the lipidation of MAP1LC3B1 to form MAP1LC3B2, which is a prerequisite for phagophore and autophagosome formation. In addition, they regulate MTOR kinase and TFEB, thereby regulating the expression of ATG genes. TRIM proteins are efficient regulators of apoptosis and are crucial for regulating cell proliferation and tumor formation. Many TRIM proteins regulate intrinsic and extrinsic apoptosis via the cell surface receptors TGFBR2, TNFRSF1A, and FAS. Mitochondria modulate the anti- and proapoptotic functions of BCL2, BAX, BAK1, and CYCS. These proteins use a multipronged approach to regulate the intrinsic and extrinsic apoptotic pathways, culminating in coordinated activation or inhibition of the initiator and executor CASPs. Furthermore, TRIMs can have a dual effect in determining cell fate and are therefore crucial for cellular homeostasis. In this review, we discuss mechanistic insights into the role of TRIM proteins in regulating autophagy and apoptosis, which can be used to better understand cellular physiology. These findings can be used to develop therapeutic interventions to prevent or treat multiple genetic and infectious diseases.

中文翻译：

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自噬和细胞凋亡的多管齐下调节：TRIM 蛋白的新作用

TRIM 蛋白的特征在于其保守的 N 端 RING、B-box 和卷曲螺旋结构域。这些蛋白质是自噬、细胞凋亡和先天免疫反应的有效调节剂，并赋予针对病毒和细菌的免疫力。TRIM 作为受体或支架蛋白发挥作用，以自噬介导的降解为目标底物。大多数 TRIM 与 BECN1-ULK1 复合物相互作用形成 TRIMosome，从而有效地将底物靶向自噬体。它们通过物理相互作用或泛素化来调节 ATG 蛋白的功能。TRIM 影响 MAP1LC3B1 的脂化形成 MAP1LC3B2，这是吞噬细胞和自噬体形成的先决条件。此外，它们还调节MTOR激酶和TFEB，从而调节ATG基因的表达。TRIM 蛋白是细胞凋亡的有效调节剂，对于调节细胞增殖和肿瘤形成至关重要。许多 TRIM 蛋白通过细胞表面受体 TGFBR2、TNFRSF1A 和 FAS 调节内在和外在细胞凋亡。线粒体调节 BCL2、BAX、BAK1 和 CYCS 的抗凋亡和促凋亡功能。这些蛋白质使用多管齐下的方法来调节内在和外在的细胞凋亡途径，最终协调激活或抑制启动子和执行子 CASP。此外，TRIM 在决定细胞命运方面具有双重作用，因此对于细胞稳态至关重要。在这篇综述中，我们讨论了 TRIM 蛋白在调节自噬和细胞凋亡中作用的机制见解，这可用于更好地理解细胞生理学。这些发现可用于开发治疗干预措施来预防或治疗多种遗传性疾病和传染病。