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TRIM Proteins Regulate Autophagy and Can Target Autophagic Substrates by Direct Recognition

机译:TRIM蛋白调节自噬并可以通过直接识别靶向自噬底物

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摘要

Autophagy, a homeostatic process whereby eukaryotic cells target cytoplasmic cargo for degradation, plays a broad role in health and disease states. Here we screened the TRIM family for roles in autophagy and found that half of TRIMs modulated autophagy. In mechanistic studies, we show that TRIMs associate with autophagy factors and act as platforms assembling ULK1 and Beclin 1 in their activated states. Furthermore, TRIM5 alpha acts as a selective autophagy receptor. Based on direct sequence-specific recognition, TRIM5 alpha delivered its cognate cytosolic target, a viral capsid protein, for autophagic degradation. Thus, our study establishes that TRIMs can function both as regulators of autophagy and as autophagic cargo receptors, and reveals a basis for selective autophagy in mammalian cells.
机译:自噬是一种稳态过程,真核细胞可通过该过程靶向细胞质货物进行降解,在健康和疾病状态中起着广泛的作用。在这里,我们筛选了TRIM家族在自噬中的作用,发现一半的TRIM调节了自噬。在机理研究中,我们表明TRIMs与自噬因子相关,并在其激活状态下充当组装ULK1和Beclin 1的平台。此外,TRIM5 alpha充当选择性自噬受体。基于直接的序列特异性识别,TRIM5 alpha交付了其同源胞质靶标(一种病毒衣壳蛋白)用于自噬降解。因此,我们的研究建立了TRIMs既可以作为自噬的调节剂又可以作为自噬货物受体,并揭示了哺乳动物细胞中选择性自噬的基础。

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