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A new mechanism of RhoA ubiquitination and degradation: Roles of SCFFBXL19 E3 ligase and Erk2 期刊论文

编号：

ffa87e72-3bc1-46d7-a27c-32cb5d7adeba
作者：

Wei, Jianxin#^[1,2]Mialki, Rachel K.^[1,2];Dong, Su(董愫)^[1,2,5]Khoo, Andrew^[1,2];Mallampalli, Rama K.^[1,2,3,4];Zhao, Yutong^[1,2];Zhao, Jing*^[1,2]
语种：

英文
期刊：

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH ISSN：0167-4889 2013 年 1833 卷 12 期 (2757 - 2764) ; DEC
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关键词：

Small GTPase protein Protein stability Ubiquitin-proteasome system Phosphorylation Cell proliferation Stress fiber
摘要：

RhoA is a small GTPase multifunctional protein that regulates cell proliferation and cytoskeletal reorganization. Regulation of its protein stability plays an important role in its biological functions. We have shown that a Skp1-Cul1-F-box (SCF) FBXL19 E3 ubiquitin ligase targets Rac1, a related member of the Rho family for ubiquitination and degradation. Here, SCFFBXL19:19 mediates RhoA ubiquitination and proteasomal degradation in lung epithelial cells. Ectopically expressed FBXL19 decreased RhoA wild type, active, and inactive forms. Cellular depletion of FBXL19 increased RhoA protein levels and extended its half-life. FBXL19 bound the small GTPase in the cytoplasm leading to RhoA ubiquitination at Lys(135). A RhoA(K135R) mutant protein was resistant to SCFFBXL19-mediated ubiquitination and degradation and exhibited a longer lifespan. Protein kinase Erk2-mediated phosphorylation of RhoA was both sufficient and required for SCFFBXL19-mediated RhoA ubiquitination and degradation. Thus, SCFFBXL19 targets RhoA for its disposal, a process regulated by Erk2. Ectopically expressed FBXL19 reduced phosphorylation of p27 and cell proliferation, a process mediated by RhoA. Further, FBXL19 cellular expression diminished lysophosphatidic acid (LPA)-induced phosphorylation of myosin light chain (MLC) and stress fiber formation. Hence, SCFFBXL19 functions as a RhoA antagonist during cell proliferation and cytoskeleton rearrangement These results provide the first evidence of an F-box protein targeting RhoA thereby modulating its cellular lifespan that impacts cell proliferation and cytoskeleton rearrangement. (c) 2013 Elsevier B.V. All rights reserved.
推荐引用方式
GB/T 7714：

Wei Jianxin,Mialki Rachel K.,Dong Su, et al. A new mechanism of RhoA ubiquitination and degradation: Roles of SCFFBXL19 E3 ligase and Erk2 [J].BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH,2013,1833(12):2757-2764.
APA：

Wei Jianxin,Mialki Rachel K.,Dong Su,Khoo Andrew,&Zhao Jing.(2013).A new mechanism of RhoA ubiquitination and degradation: Roles of SCFFBXL19 E3 ligase and Erk2 .BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH,1833(12):2757-2764.
MLA：

Wei Jianxin, et al. "A new mechanism of RhoA ubiquitination and degradation: Roles of SCFFBXL19 E3 ligase and Erk2" .BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH 1833,12(2013):2757-2764.
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