自噬
细胞生物学
泛素
泛素连接酶
袋3
ULK1
乙酰化
化学
内生
生物
生物化学
磷酸化
蛋白激酶A
细胞凋亡
基因
安普克
作者
Carmela Fusco,Barbara Mandriani,Martina Di Rienzo,Lucia Micale,Natascia Malerba,Dario Cocciadiferro,Eva Sjøttem,Bartolomeo Augello,Gabriella Maria Squeo,Maria Teresa Pellico,Ashish Jain,Terje Johansen,Gian María Fimia,Giuseppe Merla
标识
DOI:10.1016/j.bbamcr.2018.03.011
摘要
Autophagy is a catabolic process needed for maintaining cell viability and homeostasis in response to numerous stress conditions. Emerging evidence indicates that the ubiquitin system has a major role in this process. TRIMs, an E3 ligase protein family, contribute to selective autophagy acting as receptors and regulators of the autophagy proteins recognizing endogenous or exogenous targets through intermediary autophagic tags, such as ubiquitin. Here we report that TRIM50 fosters the initiation phase of starvation-induced autophagy and associates with Beclin1, a central component of autophagy initiation complex. We show that TRIM50, via the RING domain, ubiquitinates Beclin 1 in a K63-dependent manner enhancing its binding with ULK1 and autophagy activity. Finally, we found that the Lys-372 residue of TRIM50, critical for its own acetylation, is necessary for its E3 ligase activity that governs Beclin1 ubiquitination. Our study expands the roles of TRIMs in regulating selective autophagy, revealing an acetylation-ubiquitination dependent control for autophagy modulation.
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