Journal
CELLULAR SIGNALLING
Volume 25, Issue 1, Pages 144-149Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.cellsig.2012.09.023
Keywords
p27; Skp2 E3 ligase; Melanoma; Cell cycle arrest; Cyclin D1
Categories
Funding
- National Natural Science Foundation of China [31030046, 31171316]
- Ministry of Science and Technology of China [2010CB912804, 2011CB966302]
- Chinese Academy of Sciences [XDA01020104]
- Fundamental Research Funds for Central Universities [WK2060190018]
Ask authors/readers for more resources
The accumulation of unfolded proteins in the endoplasmic reticulum (ER) triggers the unfolded protein response (UPR), a stress signaling pathway. The UPR coordinates the induction of ER chaperones with decreased protein synthesis and growth arrest in G1 phase of the cell cycle. However, the molecular mechanism underlying UPR-induced G1 cell cycle arrest remains largely unknown. Here we report that activation of the UPR response by tunicamycin (TM), an ER stress inducer, leads to accumulation of p27 and G1 cell cycle arrest in melanoma cells. This accumulation of p27 is due to the inhibition on its polyubiquitination and subsequent degradation upon TM treatment. Correlated with p27 stabilization, the levels of Skp2, an E3 ligase for p27, are decreased in response to TM treatment More importantly, knockdown of p27 greatly reduces TM-induced G1 cell cycle arrest. Taken together, these data implicate p27 as a critical mediator of ER stress-induced growth arrest. (C) 2012 Elsevier Inc. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available