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A Novel Retinoblastoma Protein (RB) E3 Ubiquitin Ligase (NRBE3) Promotes RB Degradation and Is Transcriptionally Regulated by E2F1 Transcription Factor
Wang, Yingshuang1,2; Zheng, Zongfang1,2; Zhang, Jingyi1; Wang, You1,2; Kong, Ruirui1,2; Liu, Jiangying1,2; Zhang, Ying1,2; Deng, Hongkui1,3; Du, Xiaojuan1,3; Ke, Yang1,2
刊名JOURNAL OF BIOLOGICAL CHEMISTRY
2015-11-20
DOI10.1074/jbc.M115.655597
290期:47页:28200-28213
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Biochemistry & Molecular Biology
研究领域[WOS]Biochemistry & Molecular Biology
关键词[WOS]SUSCEPTIBILITY GENE-PRODUCT ; CELL-CYCLE CONTROL ; BREAST-CANCER ; TUMOR-SUPPRESSOR ; THERAPEUTIC RESPONSE ; PROTEASOME PATHWAY ; DEPENDENT DEGRADATION ; ONCOPROTEIN MDM2 ; FAMILY PROTEINS ; E7
英文摘要

Retinoblastoma protein (RB) plays critical roles in tumor suppression and is degraded through the proteasomal pathway. However, E3 ubiquitin ligases responsible for proteasome-mediated degradation of RB are largely unknown. Here we characterize a novel RB E3 ubiquitin ligase (NRBE3) that binds RB and promotes RB degradation. NRBE3 contains an LXCXE motif and bound RB in vitro. NRBE3 interacted with RB in cells when proteasome activity was inhibited. NRBE3 promoted RB ubiquitination and degradation via the ubiquitin-proteasome pathway. Importantly, purified NRBE3 ubiquitinated recombinant RB in vitro, and a U-box was identified as essential for its E3 activity. Surprisingly, NRBE3 was transcriptionally activated by E2F1/DP1. Consequently, NRBE3 affected the cell cycle by promoting G1/S transition. Moreover, NRBE3 was up-regulated in breast cancer tissues. Taken together, we identified NRBE3 as a novel ubiquitin E3 ligase for RB that might play a role as a potential oncoprotein in human cancers.

语种英语
WOS记录号WOS:000365761900015
项目编号30571038 ; 81372222 ; IRT13001 ; 7122032
资助机构National Natural Science Foundation of China ; Innovation team of the Ministry of Education ; Beijing Municipal Natural Science Foundation
引用统计
被引频次:2[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/61606
专题北京大学临床肿瘤学院
北京大学医学部管理机构_医学部
北京大学基础医学院
北京大学临床肿瘤学院_遗传学研究室
作者单位1.Peking Univ, Beijing Canc Hosp & Inst, Sch Oncol, Key Lab Carcinogenesis & Translat Res,Minist Educ, Beijing 100142, Peoples R China
2.Peking Univ, Beijing Canc Hosp & Inst, Sch Oncol, Genet Lab, Beijing 100142, Peoples R China
3.Peking Univ, Hlth Sci Ctr, Sch Basic Med Sci, Dept Cell Biol, Beijing 100191, Peoples R China
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Wang, Yingshuang,Zheng, Zongfang,Zhang, Jingyi,et al. A Novel Retinoblastoma Protein (RB) E3 Ubiquitin Ligase (NRBE3) Promotes RB Degradation and Is Transcriptionally Regulated by E2F1 Transcription Factor[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2015,290(47):28200-28213.
APA Wang, Yingshuang.,Zheng, Zongfang.,Zhang, Jingyi.,Wang, You.,Kong, Ruirui.,...&Ke, Yang.(2015).A Novel Retinoblastoma Protein (RB) E3 Ubiquitin Ligase (NRBE3) Promotes RB Degradation and Is Transcriptionally Regulated by E2F1 Transcription Factor.JOURNAL OF BIOLOGICAL CHEMISTRY,290(47),28200-28213.
MLA Wang, Yingshuang,et al."A Novel Retinoblastoma Protein (RB) E3 Ubiquitin Ligase (NRBE3) Promotes RB Degradation and Is Transcriptionally Regulated by E2F1 Transcription Factor".JOURNAL OF BIOLOGICAL CHEMISTRY 290.47(2015):28200-28213.
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