Back to Search
Start Over
RACK1 and CIS Mediate the Degradation of BimEL in Cancer CeIIs.
- Source :
-
Journal of Biological Chemistry . 6/13/2008, Vol. 283 Issue 24, p16416-16426. 11p. 2 Graphs. - Publication Year :
- 2008
-
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 RACK 1 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. [ABSTRACT FROM AUTHOR]
- Subjects :
- *CANCER cells
*APOPTOSIS
*LIGASES
*BREAST cancer
*CELL lines
Subjects
Details
- Language :
- English
- ISSN :
- 00219258
- Volume :
- 283
- Issue :
- 24
- Database :
- Academic Search Index
- Journal :
- Journal of Biological Chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 32691891
- Full Text :
- https://doi.org/10.1074/jbc.M802360200