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FBXL20-mediated Vps34 ubiquitination as a p53 controlled checkpoint in regulating autophagy and receptor degradation
Alternative TitleFBXL20-mediated Vps34 ubiquitination as a p53 controlled checkpoint in regulating autophagy and receptor degradation
XIAO JUAN1; ZHANG TAO1; XU DAICHAO1; WANG HUIBING1; CAI YU1; JIN TAIJIE1; LIU MIN1; JIN MINGZHI1; WU KEJIA1; Yuan JY(袁钧瑛)1
2015
Source PublicationGenes Dev.
Volume29Issue:2Pages:184-196
AbstractVacuolar protein-sorting 34 (Vps34), the catalytic subunit in the class III PtdIns3 (phosphatidylinositol 3) kinase complexes, mediates the production of PtdIns3P, a key intracellular lipid involved in regulating autophagy and receptor degradation. However, the signal transduction pathways by which extracellular signals regulate Vps34 complexes and the downstream cellular mechanisms are not well understood. Here we show that DNA damage-activated mitotic arrest and CDK activation lead to the phosphorylation of Vps34, which provides a signal to promote its ubiquitination and proteasomal degradation mediated by FBXL20 (an F-box protein) and the associated Skp1 (S-phase kinase-associated protein-1)-Cullin1 complex, leading to inhibition of autophagy and receptor endocytosis. Furthermore, we show that the expression of FBXL20 is regulated by p53-dependent transcription. Our study provides a molecular pathway by which DNA damage regulates Vps34 complexes and its downstream mechanisms, including autophagy and receptor endocytosis, through SCF (Skp1-Cul1-F-box)-mediated ubiquitination and degradation. Since the expression of FBXL20 is regulated by p53-dependent transcription, the control of Vps34 ubiquitination and proteasomal degradation by FBXL20 and the associated SCF complex expression provides a novel checkpoint for p53 to regulate autophagy and receptor degradation in DNA damage response.
Subtype论文
Subject Area生命有机化学
DOI10.1101/gad.252528.114
URL查看原文
Indexed BySCI
Language英语
WOS IDWOS:000347969500007
Citation statistics
Cited Times:23[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://ir.sioc.ac.cn/handle/331003/39478
Collection生命有机化学国家重点实验室
Affiliation1.中科院上海有机化学研究所, 生物与化学交叉研究中心
2.美国哈佛大学
Recommended Citation
GB/T 7714
XIAO JUAN,ZHANG TAO,XU DAICHAO,et al. FBXL20-mediated Vps34 ubiquitination as a p53 controlled checkpoint in regulating autophagy and receptor degradation[J]. Genes Dev.,2015,29(2):184-196.
APA XIAO JUAN.,ZHANG TAO.,XU DAICHAO.,WANG HUIBING.,CAI YU.,...&袁钧瑛.(2015).FBXL20-mediated Vps34 ubiquitination as a p53 controlled checkpoint in regulating autophagy and receptor degradation.Genes Dev.,29(2),184-196.
MLA XIAO JUAN,et al."FBXL20-mediated Vps34 ubiquitination as a p53 controlled checkpoint in regulating autophagy and receptor degradation".Genes Dev. 29.2(2015):184-196.
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