Am J Physiol Cell Physiol AJP: Cell Physiology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Am J Physiol Cell Physiol 296: C1086-C1097, 2009. First published March 11, 2009; doi:10.1152/ajpcell.00675.2008
0363-6143/09 $8.00
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
296/5/C1086    most recent
00675.2008v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Prokopenko, O.
Right arrow Articles by Mirochnitchenko, O.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Prokopenko, O.
Right arrow Articles by Mirochnitchenko, O.

MEMBRANE TRANSPORTERS, ION CHANNELS, AND PUMPS

Ischemia-reperfusion-inducible protein modulates cell sensitivity to anticancer drugs by regulating activity of efflux transporter

Olga Prokopenko and Oleg Mirochnitchenko

Department of Biochemistry, Robert Wood Johnson Medical School, Piscataway, New Jersey

Submitted 30 December 2008 ; accepted in final form 9 March 2009

Human ischemia-reperfusion-inducible protein (hIRIP) or hYrdC belongs to the SUA5/YrdC/YciO protein family and affects activity of a variety of cellular transporters. We observed that overexpression of wild-type or dominant-negative mutant of hIRIP protein affects the cellular sensitivity to anticancer drugs with different mechanisms of toxicity. Here we investigated in detail the effect of hIRIP on cell sensitivity to doxorubicin and show that hIRIP inhibits the drug efflux. Multidrug-resistant P-glycoprotein was identified as one of the target transporters. IRIP does not influence P-glycoprotein biosynthesis but affects its processing and promotes degradation. We also show that P-glycoprotein is associated with COP-{alpha}, one of the proteins of the COPI complex. This interaction is sensitive to the level of hIRIP expression. These findings suggest that hIRIP expression can regulate cargo assembly and function of efflux transporters, including P-glycoprotein, which mediates one of the most common mechanisms of the multidrug resistance.

transport; P-glycoprotein


Address for reprint requests and other correspondence: O. Mirochnitchenko, Dept. of Biochemistry, UMDNJ-RWJMS, 675 Hoes Lane, Piscataway, NJ 08854 (e-mail: mirochol{at}umdnj.edu)






HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online
Copyright © 2009 by the American Physiological Society.