Selective MAP1LC3C (LC3C) autophagy requires noncanonical regulators and the C-terminal peptide
| Autor: | Michael J Newbold, Anurag Paul, Jun-Lin Guan, Megan E Bischoff, Jarek Meller, Nicholas J Talbot, Adam D Price, Yuanwei Zang, Maria F. Czyzyk-Krzeska, Birgit Ehmer, Johnson Chu, David R. Plas |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Autophagy-Related Proteins
UVRAG Lipid-anchored protein Peptide Biology Protein Serine-Threonine Kinases ESCRT Article 03 medical and health sciences Phosphatidylinositol 3-Kinases 0302 clinical medicine Cancer stem cell Autophagy TSG101 Humans 030304 developmental biology Cancer chemistry.chemical_classification 0303 health sciences Endosomal Sorting Complexes Required for Transport Tumor Suppressor Proteins Autophagosomes Cell Biology Cell biology Cell Death and Autophagy DNA-Binding Proteins Midbody chemistry Proteolysis Peptides Microtubule-Associated Proteins 030217 neurology & neurosurgery HeLa Cells Transcription Factors |
| Zdroj: | The Journal of Cell Biology |
| ISSN: | 1540-8140 0021-9525 |
| Popis: | The work identifies a noncanonical autophagic program mediated by the hominid-specific LC3C paralog functioning downstream from the von Hippel–Lindau tumor suppressor. The program targets for lysosomal degradation postdivision midbodies in a mechanism requiring FIP200/ATG13/ULK3 and UVRAG/RUBCN/PIK3C2A/BECN1 complexes as well as the C-terminal peptide of LC3C. 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|