Ubiquitination of the PI3-kinase VPS-34 promotes VPS-34 stability and phagosome maturation

• DOI: 10.1083/jcb.201705116
• Publication Date: 2017-11-01T13:15:28Z
• Authors: Jinchao Liu; Meijiao Li; Lin Li; She Chen; Xiaochen Wang
• Keywords: 0301 basic medicine; Ubiquitin; Ubiquitin-Protein Ligases; Ubiquitination; Apoptosis; Class III Phosphatidylinositol 3-Kinases; Phosphatidylinositol 3-Kinases; 03 medical and health sciences; Phagocytosis; Phagosomes; Ubiquitin-Conjugating Enzymes; Animals; Caenorhabditis elegans; Caenorhabditis elegans Proteins; Research Articles

Apoptotic cells generated by programmed cell death are engulfed phagocytes and enclosed within membrane-bound phagosomes. Maturation of apoptotic cell–containing phagosomes leads to formation phagolysosomes where corpses degraded. The class III phosphatidylinositol 3-kinase (PI3-kinase) VPS-34 coordinates with PIKI-1, a II PI3-kinase, produce PtdIns3P on phagosomes, thus promoting phagosome closure maturation. Here, we identified UBC-13, an E2 ubiquitin–conjugating enzyme that functions in the same pathway but parallel PIKI-1 regulate generation Loss ubc-13 affects early steps maturation, causing accumulation corpses. We found UBC-13 UEV-1, noncatalytic variant, CHN-1, U-box–containing E3 ubiquitin ligase, catalyze K63-linked poly-ubiquitination both vitro Caenorhabditis elegans. ubc-13, uev-1, or chn-1 disrupts modification causes significantly reduced protein levels. Our data suggest serves as general mechanism modulate stability multiple processes.