期刊
CELLULAR SIGNALLING
卷 22, 期 3, 页码 553-563出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.cellsig.2009.11.012
关键词
c-Cbl; TRAIL; TRAIL receptors; TRAIL resistance
类别
资金
- NCl [CA95191, CA96989, CA121395, CA113263]
- DOD Prostate Program [PC020530, PC040833]
- Susan G. Komen Breast Cancer Foundation [BCTR60306]
- Samuel & Emma Winters Foundation
- Ministry of Education, Science and Technology [2009-0071809]
- Yonsei University College of Medicine [2009-0113]
- Ministry of Commerce, Industry, and Energy of Korea [990-14-05]
- National Research Foundation of Korea [2009-0071809] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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 4 h 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 (C) 2009 Elsevier Inc. All rights reserved.
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