期刊
JOURNAL OF CELL BIOLOGY
卷 217, 期 1, 页码 347-360出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.201705116
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资金
- National Institutes of Health Office of Research Infrastructure Programs [P40OD010440]
- Chinese Ministry of Science and Technology [2016YFA0500203]
- National Natural Science Foundation of China [31325015, 3163001]
- Strategic Priority Research Program of the Chinese Academy of Sciences [XDB19000000]
- National Basic Research Program of China [2014CB849702]
- International Early Career Scientist grant from the Howard Hughes Medical Institute
Apoptotic cells generated by programmed cell death are engulfed by phagocytes and enclosed within membrane-bound phagosomes. Maturation of apoptotic cell-containing phagosomes leads to formation of phagolysosomes where cell corpses are degraded. The class III phosphatidylinositol 3-kinase (PI3-kinase) VPS-34 coordinates with PIKI-1, a class II PI3-kinase, to produce PtdIns3P on phagosomes, thus promoting phagosome closure and maturation. Here, we identified UBC-13, an E2 ubiquitin-conjugating enzyme that functions in the same pathway with VPS-34 but in parallel to PIKI-1 to regulate PtdIns3P generation on phagosomes. Loss of ubc-13 affects early steps of phagosome maturation, causing accumulation of cell corpses. We found that UBC-13 functions with UEV-1, a noncatalytic E2 variant, and CHN-1, a U-box-containing E3 ubiquitin ligase, to catalyze K63-linked poly-ubiquitination on VPS-34 both in vitro and in Caenorhabditis elegans. Loss of ubc-13, uev-1, or chn-1 disrupts ubiquitin modification of VPS-34 and causes significantly reduced VPS-34 protein levels. Our data suggest that K63-linked ubiquitin modification serves as a general mechanism to modulate VPS-34 stability in multiple processes.
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