RACK1 and CIS Mediate the Degradation of BimEL in Cancer Cells

Weizhou Zhang; George Zhi Cheng; Jianli Gong; Ulrich Hermanto; Cong Susan Zong; Joseph Chan; Jin Quan Cheng; Lu-Hai Wang

doi:10.1074/jbc.M802360200

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RACK1 and CIS Mediate the Degradation of BimEL in Cancer Cells

Journal article

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RACK1 and CIS Mediate the Degradation of BimEL in Cancer Cells

Weizhou Zhang, George Zhi Cheng, Jianli Gong, Ulrich Hermanto, Cong Susan Zong, Joseph Chan, Jin Quan Cheng and Lu-Hai Wang

The Journal of biological chemistry, Vol.283(24), pp.16416-16426

06/13/2008

DOI: 10.1074/jbc.M802360200

PMCID: PMC2423247

PMID: 18420585

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Abstract

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.

Details

Title: Subtitle: RACK1 and CIS Mediate the Degradation of BimEL in Cancer Cells
Creators: Weizhou Zhang - Department of Microbiology, Mount Sinai School of Medicine, New York, New York 10029, the Departments of
George Zhi Cheng - Department of Microbiology, Mount Sinai School of Medicine, New York, New York 10029, the Departments of
Jianli Gong - Department of Microbiology, Mount Sinai School of Medicine, New York, New York 10029, the Departments of
Ulrich Hermanto - Radiology
Cong Susan Zong - Molecular and Cellular Oncology, MD Anderson Cancer Center, University of Texas, Houston, Texas 77030
Joseph Chan - Department of Microbiology, Mount Sinai School of Medicine, New York, New York 10029, the Departments of
Jin Quan Cheng - Department of Pathology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida 33612
Lu-Hai Wang - Department of Microbiology, Mount Sinai School of Medicine, New York, New York 10029, the Departments of
Resource Type: Journal article
Publication Details: The Journal of biological chemistry, Vol.283(24), pp.16416-16426
DOI: 10.1074/jbc.M802360200
PMID: 18420585
PMCID: PMC2423247
NLM abbreviation: J Biol Chem
ISSN: 0021-9258
eISSN: 1083-351X
Publisher: Elsevier Inc
Grant note: CA29339 / National Institutes of Health (https://doi.org/10.13039/100000002) New York State Department of Health (https://doi.org/10.13039/100004856)
Language: English
Date published: 06/13/2008
Academic Unit: Radiation Oncology
Record Identifier: 9984083872502771

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