期刊
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
卷 518, 期 2, 页码 103-110出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.abb.2011.12.023
关键词
von Hippel-Lindau tumor suppressor; Heterochromatin protein 1; Interaction; Mass spectrometry; Renal carcinoma
资金
- NIH [CA125020, CA054174]
Inactivation of the von Hippel-Lindau (VHL) tumor suppressor is associated with renal carcinoma, hemangioblastoma and pheochromocytoma. The VHL protein is a component of a ubiquitin ligase complex that ubiquitinates and degrades hypoxia inducible factor-alpha (HIF-alpha). Degradation of HIF-alpha by VHL is proposed to suppress tumorigenesis and tumor angiogenesis. Several lines of evidence also suggest important roles for HIF-independent VHL functions in tumor suppression and other biological processes. Using GST-VHL pull-down experiment and mass spectrometry, we detected an interaction between VHL and heterochromatin protein 1 (HP1). We identified a conserved HP1-binding motif (PXVXL) in the beta domain of VHL, which is disrupted in a renal carcinoma-associated P81S mutant. We show that the VHL P81S mutant displays reduced binding to HP1, yet retains the ability to interact with elongin B, elongin C, and cullin 2 and is fully capable of degrading HIF-a. We also demonstrate that HP1 increases the chromatin association of VHL. These results suggest a role for the VHL-HP1 interaction in VHL chromatin targeting. (C) 2011 Elsevier Inc. All rights reserved.
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