Chong Wang, Haowen Xiao, Jie Ma, Yuanyuan Zhu, Jian Yu, Ling Sun, Hui Sun, Yanfang Liu, Changjiang Jin, He Huang
Department of Hematology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
Biochemical and biophysical research communications 2013 May 17The telomeric repeat binding protein 1 (TRF1) is a major factor of the mammalian telosome/shelterin and negatively regulates telomere length by inhibiting access of telomerase at telomere termini in telomerase-positive cells. In telomerase-negative cancer cells, TRF1 also plays a critical role in the mechanism called alternative lengthening of telomeres (ALT) and is essential for formation of the ALT-associated PML bodies (APBs). It was reported that TRF1 can be degraded by the ubiquitin-proteasome pathway, involving in two regulation factors, Fbx4 and RLIM. Here, we reported that β-TrCP1, a member of the F-box family protein with ubiquitin ligase activity, is a novel TRF1-associating protein. β-TrCP1 interacts with TRF1 in vivo and in vitro and promotes its ubiquitination. Overexpression of β-TrCP1 reduces endogenous TRF1 protein levels, while inhibition of β-TrCP1 by siRNA stabilizes TRF1. Moreover, we found that β-TrCP1 is essential for regulation of promyelocytic leukemia body recruitment of TRF1 in U2OS cells. These results reveal that β-TrCP1 is involved in the negative regulation of TRF1 and represents a new pathway for APB formation in telomerase-negative cells. Copyright © 2013 Elsevier Inc. All rights reserved.
Chong Wang, Haowen Xiao, Jie Ma, Yuanyuan Zhu, Jian Yu, Ling Sun, Hui Sun, Yanfang Liu, Changjiang Jin, He Huang. The F-box protein β-TrCP promotes ubiquitination of TRF1 and regulates the ALT-associated PML bodies formation in U2OS cells. Biochemical and biophysical research communications. 2013 May 17;434(4):728-34
PMID: 23583392
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