DNA Damage Induces the Accumulation of Tiam1 by Blocking   beta-TrCP-dependent Degradation

doi:10.1074/jbc.M114.553388

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	DNA Damage Induces the Accumulation of Tiam1 by Blocking beta-TrCP-dependent Degradation
	Zhu, Guixin ; Fan, Zhongyun ; Ding, Miao ; Mu, Libing ; Liang, Juan ; Ding, Yajie ; Fu, Yu ; Huang, Binlu ; Wu, Wei
刊名	journal of biological chemistry
	2014
关键词	Apoptosis DNA Damage E3 Ubiquitin Ligase c-Jun N-terminal Kinase (JNK) Rac1 Tiam1 Chemotherapy RAC ACTIVATOR TIAM1 EXCHANGE FACTOR TIAM1 E3 UBIQUITIN LIGASES INDUCED APOPTOSIS KINASE ACTIVATION DESTRUCTION MOTIF JNK ACTIVATION RHO-GTPASES CELLS PHOSPHORYLATION
DOI	10.1074/jbc.M114.553388
英文摘要	The Rac1/JNK cascade plays important roles in DNA damage-induced apoptosis. However, how this cascade is activated upon DNA damage remains to be fully understood. We show here that, in untreated cells, Tiam1, a Rac1-specific guanine nucleotide exchange factor, is phosphorylated by casein kinase 1 (CK1) at its C terminus, leading to Skp, Cullin, F-box-containing(-TrCP) recognition, ubiquitination, and proteasome-mediated degradation. Upon DNA-damaging anticancer drug treatment, CK1/-TrCP-mediated Tiam1 degradation is abolished, and the accumulated Tiam1 contributes to downstream activation of Rac1/JNK. Consistently, tumor cells overexpressing Tiam1 are hypersensitive to DNA-damaging drug treatment. In xenograft mice, Tiam1-high cells are more susceptible to doxorubicin treatment. Thus, our results uncover that inhibition of proteasome-mediated Tiam1 degradation is an upstream event leading to Rac1/JNK activation and cell apoptosis in response to DNA-damaging drug treatment.; Biochemistry & Molecular Biology; SCI(E); EI; PubMed; 3; ARTICLE; wwu@mail.tsinghua.edu.cn; 22; 15482-15494; 289
语种	英语
内容类型	期刊论文
源URL	[http://ir.pku.edu.cn/handle/20.500.11897/342400]
专题	生命科学学院
推荐引用方式 GB/T 7714	Zhu, Guixin,Fan, Zhongyun,Ding, Miao,et al. DNA Damage Induces the Accumulation of Tiam1 by Blocking beta-TrCP-dependent Degradation[J]. journal of biological chemistry,2014.
APA	Zhu, Guixin.,Fan, Zhongyun.,Ding, Miao.,Mu, Libing.,Liang, Juan.,...&Wu, Wei.(2014).DNA Damage Induces the Accumulation of Tiam1 by Blocking beta-TrCP-dependent Degradation.journal of biological chemistry.
MLA	Zhu, Guixin,et al."DNA Damage Induces the Accumulation of Tiam1 by Blocking beta-TrCP-dependent Degradation".journal of biological chemistry (2014).