RRC ID 51515
著者 Liu J, Li M, Li L, Chen S, Wang X.
タイトル Ubiquitination of the PI3-kinase VPS-34 promotes VPS-34 stability and phagosome maturation.
ジャーナル J Cell Biol
Abstract 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.
巻・号 217(1)
ページ 347-360
公開日 2018-1-2
DOI 10.1083/jcb.201705116
PII jcb.201705116
PMID 29092895
PMC PMC5748982
MeSH Animals Apoptosis / physiology Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Class III Phosphatidylinositol 3-Kinases / metabolism* Phagocytosis / immunology Phagosomes / metabolism* Phosphatidylinositol 3-Kinases / metabolism Ubiquitin / metabolism Ubiquitin-Conjugating Enzymes / genetics Ubiquitin-Conjugating Enzymes / metabolism* Ubiquitin-Protein Ligases / genetics Ubiquitin-Protein Ligases / metabolism* Ubiquitination*
IF 8.811
引用数 8
リソース情報
線虫 tm2692 tm3066 tm3546