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选择性 MAP1LC3C（LC3C）自噬需要非典型调节因子和 C 端肽。

Selective MAP1LC3C (LC3C) autophagy requires noncanonical regulators and the C-terminal peptide.

机构信息

Department of Cancer Biology, University of Cincinnati College of Medicine, Cincinnati, OH.

Department of Urology, Qilu Hospital, Shandong University, Jinan, People's Republic of China.

出版信息

J Cell Biol. 2021 Jul 5;220(7). doi: 10.1083/jcb.202004182. Epub 2021 May 14.

DOI:10.1083/jcb.202004182
PMID:33988680
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8129795/
Abstract

LC3s are canonical proteins necessary for the formation of autophagosomes. We have previously established that two paralogs, LC3B and LC3C, have opposite activities in renal cancer, with LC3B playing an oncogenic role and LC3C a tumor-suppressing role. LC3C is an evolutionary late gene present only in higher primates and humans. Its most distinct feature is a C-terminal 20-amino acid peptide cleaved in the process of glycine 126 lipidation. Here, we investigated mechanisms of LC3C-selective autophagy. LC3C autophagy requires noncanonical upstream regulatory complexes that include ULK3, UVRAG, RUBCN, PIK3C2A, and a member of ESCRT, TSG101. We established that postdivision midbody rings (PDMBs) implicated in cancer stem-cell regulation are direct targets of LC3C autophagy. LC3C C-terminal peptide is necessary and sufficient to mediate LC3C-dependent selective degradation of PDMBs. This work establishes a new noncanonical human-specific selective autophagic program relevant to cancer stem cells.

摘要

LC3s 是形成自噬体所必需的经典蛋白。我们之前已经证实，两种同源物 LC3B 和 LC3C 在肾癌中具有相反的作用，LC3B 发挥致癌作用，而 LC3C 发挥肿瘤抑制作用。LC3C 是一种进化后期的基因，仅存在于高等灵长类动物和人类中。它最显著的特征是在甘氨酸 126 脂化过程中被切割的 C 末端 20 个氨基酸肽。在这里，我们研究了 LC3C 选择性自噬的机制。LC3C 自噬需要非典型的上游调节复合物，包括 ULK3、UVRAG、RUBCN、PIK3C2A 和 ESCRT 的一个成员 TSG101。我们确定了参与癌症干细胞调节的分裂后中期体环 (PDMBs) 是 LC3C 自噬的直接靶点。LC3C C 末端肽是介导 LC3C 依赖性 PDMBs 选择性降解所必需和充分的。这项工作建立了一个新的与癌症干细胞相关的非典型人类特异性选择性自噬程序。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e084/8129795/b3a5cbdde5af/JCB_202004182_Fig9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e084/8129795/41c9cccc7fb0/JCB_202004182_Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e084/8129795/5e3469453b69/JCB_202004182_FigS1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e084/8129795/58294f69548f/JCB_202004182_Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e084/8129795/e269a6951fee/JCB_202004182_FigS2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e084/8129795/e0aae2a27dff/JCB_202004182_Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e084/8129795/6733a807bcf0/JCB_202004182_Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e084/8129795/f82e01353060/JCB_202004182_Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e084/8129795/21aeb9363b12/JCB_202004182_FigS3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e084/8129795/a7004fb10fdd/JCB_202004182_Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e084/8129795/c57258189063/JCB_202004182_FigS4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e084/8129795/ee991e6cee7a/JCB_202004182_Fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e084/8129795/2069c5a9be87/JCB_202004182_FigS5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e084/8129795/2b94c8a538ab/JCB_202004182_Fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e084/8129795/b3a5cbdde5af/JCB_202004182_Fig9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e084/8129795/41c9cccc7fb0/JCB_202004182_Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e084/8129795/5e3469453b69/JCB_202004182_FigS1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e084/8129795/58294f69548f/JCB_202004182_Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e084/8129795/e269a6951fee/JCB_202004182_FigS2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e084/8129795/e0aae2a27dff/JCB_202004182_Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e084/8129795/6733a807bcf0/JCB_202004182_Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e084/8129795/f82e01353060/JCB_202004182_Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e084/8129795/21aeb9363b12/JCB_202004182_FigS3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e084/8129795/a7004fb10fdd/JCB_202004182_Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e084/8129795/c57258189063/JCB_202004182_FigS4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e084/8129795/ee991e6cee7a/JCB_202004182_Fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e084/8129795/2069c5a9be87/JCB_202004182_FigS5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e084/8129795/2b94c8a538ab/JCB_202004182_Fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e084/8129795/b3a5cbdde5af/JCB_202004182_Fig9.jpg

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