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c-Cbl-mediated degradation of TRAIL receptors is responsible for the development of the early phase of TRAIL resistance

Authors
 Jae J. Song  ;  Miroslaw Jerzy Szczepanski#  ;  So Young Kim  ;  Joo-Hang Kim  ;  Jee Young An  ;  Yong Tae Kwon  ;  Marco A. Alcala Jr  ;  David L. Bartlett  ;  Yong J. Lee 
Citation
 CELLULAR SIGNALLING, Vol.22(3) : 553-563, 2010 
Journal Title
 CELLULAR SIGNALLING 
ISSN
 0898-6568 
Issue Date
2010
MeSH
Amino Acid Substitution ; Cell Line, Tumor ; Humans ; Mutagenesis, Site-Directed ; Proto-Oncogene Proteins c-cbl/genetics ; Proto-Oncogene Proteins c-cbl/metabolism ; Proto-Oncogene Proteins c-cbl/physiology* ; RNA, Small Interfering/metabolism ; Receptors, TNF-Related Apoptosis-Inducing Ligand/metabolism* ; TNF-Related Apoptosis-Inducing Ligand/pharmacology* ; Ubiquitination
Keywords
c-Cbl ; TRAIL ; TRAIL receptors ; TRAIL resistance
Abstract
We previously reported two modes of development of acquired TRAIL resistance: early phase and late phase [1]. In these studies, we observed that greater Akt activity and the expression of Bcl-xL were related mainly to the late phase of acquired TRAIL resistance. Recently we became aware of a possible mechanism of early phase TRAIL resistance development through internalization and degradation of TRAIL receptors (DR4 and DR5). Our current studies demonstrate that TRAIL receptors rapidly diminish at the membrane as well as the cytoplasm within 4h after TRAIL exposure, but recover completely after one or two days. Our studies also reveal that Cbl, a ubiquitously expressed cytoplasmic adaptor protein, is responsible for the rapid degradation of TRAIL receptors; Cbl binds to them and induces monoubiquitination of these receptors concurrent with their degeneration soon after TRAIL exposure, creating the early phase of acquired TRAIL resistance.
Files in This Item:
T201000074.pdf Download
DOI
10.1016/j.cellsig.2009.11.012
Appears in Collections:
5. Research Institutes (연구소) > Institute for Cancer Research (암연구소) > 1. Journal Papers
Yonsei Authors
Song, Jae Jin(송재진) ORCID logo https://orcid.org/0000-0001-8183-9550
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/100424
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