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ARMC5 is part of an RPB1-specific ubiquitin ligase implicated in adrenal hyperplasia

文献类型：期刊论文

作者Lao, Linjiang14; Bourdeau, Isabelle13,14; Gagliardi, Lucia10,11,12,15; He, Xiao14; Shi, Wei2,14; Hao, Bingbing9; Tan, Minjia9; Hu, Yan1,14; Peng, Junzheng14; Coulombe, Benoit7,8
刊名NUCLEIC ACIDS RESEARCH
出版日期2022-06-10
页码25
ISSN号0305-1048
DOI10.1093/nar/gkac483
通讯作者Luo, Hongyu(hongyu.luo@umontreal.ca) ; Wu, Jiangping(jianping.wu@umontreal.ca)
英文摘要ARMC5 is implicated in several pathological conditions, but its function remains unknown. We have previously identified CUL3 and RPB1 (the largest subunit of RNA polymerase II (Pol II) as potential ARMC5-interacting proteins. Here, we show that ARMC5, CUL3 and RBX1 form an active E3 ligase complex specific for RPB1. ARMC5, CUL3, and RBX1 formed an active E3 specific for RPB1. Armc5 deletion caused a significant reduction in RPB1 ubiquitination and an increase in an accumulation of RPB1, and hence an enlarged Pol II pool in normal tissues and organs. The compromised RPB1 degradation did not cause generalized Pol II stalling nor depressed transcription in the adrenal glands but did result in dysregulation of a subset of genes, with most upregulated. We found RPB1 to be highly expressed in the adrenal nodules from patients with primary bilateral macronodular adrenal hyperplasia (PBMAH) harboring germline ARMC5 mutations. Mutant ARMC5 had altered binding with RPB1. In summary, we discovered that wildtype ARMC5 was part of a novel RPB1-specific E3. ARMC5 mutations resulted in an enlarged Pol II pool, which dysregulated a subset of effector genes. Such an enlarged Pol II pool and gene dysregulation was correlated to adrenal hyperplasia in humans and KO mice.
WOS关键词RNA-POLYMERASE-II ; E3 LIGASE ; TUMOR-SUPPRESSOR ; LARGE SUBUNIT ; POL-II ; TRANSCRIPTION ; PROTEIN ; MUTATIONS ; GENES ; UBIQUITYLATION
资助项目Canadian Institutes of Health Research[PJT180284] ; Arthritis Society of Canada[SOG-21-0158] ; Natural Science and Engineering Research Council of Canada[PGPIN-2017-04790] ; FRQS ; J.-Louis Levesque Foundation
WOS研究方向Biochemistry & Molecular Biology
语种英语
出版者OXFORD UNIV PRESS
WOS记录号WOS:000809115800001
源URL[http://119.78.100.183/handle/2S10ELR8/301422]  
专题中国科学院上海药物研究所
通讯作者Luo, Hongyu; Wu, Jiangping
作者单位1.State Univ New York Downstate Hlth Sci Univ, Dept Anesthesiol, 450 Clarkson Ave, Brooklyn, NY 11203 USA
2.Zhejiang Univ, Sch Med, Childrens Hosp, Dept Neonatol, Hangzhou 310003, Peoples R China
3.Ctr Hosp Univ Montreal CHUM, Nephrol Div, Montreal, PQ H2X 0A9, Canada
4.Univ South Australia, UniSA Clin & Hlth Sci, Adelaide, SA 5001, Australia
5.Univ South Australia, Adelaide, SA 5001, Australia
6.SA Pathol, Ctr Canc Biol, Adelaide, SA 5001, Australia
7.Univ Montreal, Dept Biochem & Mol Med, Montreal, PQ, Canada
8.Inst Rech Clin Montreal, Dept Translat Prote, Montreal, PQ, Canada
9.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China
10.Queen Elizabeth Hosp, Endocrine & Diabet Unit, Adelaide, SA 5011, Australia
推荐引用方式
GB/T 7714		 Lao, Linjiang,Bourdeau, Isabelle,Gagliardi, Lucia,et al. ARMC5 is part of an RPB1-specific ubiquitin ligase implicated in adrenal hyperplasia[J]. NUCLEIC ACIDS RESEARCH,2022:25.
APA Lao, Linjiang.,Bourdeau, Isabelle.,Gagliardi, Lucia.,He, Xiao.,Shi, Wei.,...&Wu, Jiangping.(2022).ARMC5 is part of an RPB1-specific ubiquitin ligase implicated in adrenal hyperplasia.NUCLEIC ACIDS RESEARCH,25.
MLA Lao, Linjiang,et al."ARMC5 is part of an RPB1-specific ubiquitin ligase implicated in adrenal hyperplasia".NUCLEIC ACIDS RESEARCH (2022):25.

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来源：上海药物研究所

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