Document Detail

RACK1 and CIS mediate the degradation of BimEL in cancer cells.
MedLine Citation:
PMID:  18420585     Owner:  NLM     Status:  MEDLINE    
RACK1 is a 7-WD motif-containing protein with numerous downstream effectors regulating various cellular functions. Using a yeast two-hybrid screen, we identified dynein light chain 1 as a novel interacting partner of RACK1. Additionally, we demonstrated that RACK1 formed a complex with DLC1 and Bim, specifically BimEL, in the presence of apoptotic agents. Upon paclitaxel treatment, RACK1, DLC1, and CIS mediated the degradation of BimEL through the ElonginB/C-Cullin2-CIS ubiquitin-protein isopeptide ligase complex. We further showed that RACK1 conferred paclitaxel resistance to breast cancer cells in vitro and in vivo. Finally, we observed an inverse correlation between CIS and BimEL levels in both ovarian and breast cancer cell lines and specimens. Our study suggests a role of RACK1 in protecting cancer cells from apoptosis by regulating the degradation of BimEL, which together with CIS could play an important role of drug resistance in chemotherapy.
Weizhou Zhang; George Zhi Cheng; Jianli Gong; Ulrich Hermanto; Cong Susan Zong; Joseph Chan; Jin Quan Cheng; Lu-Hai Wang
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2008-04-17
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  283     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2008 Jun 
Date Detail:
Created Date:  2008-06-09     Completed Date:  2008-07-24     Revised Date:  2014-05-09    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  16416-26     Citation Subset:  IM    
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MeSH Terms
Apoptosis Regulatory Proteins / metabolism
Drug Resistance, Neoplasm
GTP-Binding Proteins / metabolism*
Membrane Proteins / metabolism
Mice, Inbred BALB C
Mice, Nude
Models, Biological
Neoplasm Proteins / metabolism*
Neoplasms / drug therapy
Neuropeptides / metabolism*
Proto-Oncogene Proteins / metabolism
Receptors, Cell Surface / metabolism*
Suppressor of Cytokine Signaling Proteins / metabolism*
Grant Support
Reg. No./Substance:
0/Apoptosis Regulatory Proteins; 0/Bcl-2-like protein 11; 0/GNB2L1 protein, human; 0/Gnb2-rs1 protein, mouse; 0/Membrane Proteins; 0/Neoplasm Proteins; 0/Neuropeptides; 0/Proto-Oncogene Proteins; 0/Receptors, Cell Surface; 0/Suppressor of Cytokine Signaling Proteins; 0/cytokine inducible SH2-containing protein; EC 3.6.1.-/GTP-Binding Proteins

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