The interaction of the von Hippel-Lindau tumor suppressor and heterochromatin protein 1.
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-α (HIF-α). Degradation of HIF-α 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 β 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-α. 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.
Mesh Terms:
Amino Acid Motifs, Amino Acid Substitution, Animals, Cell Line, Chromatin, Chromosomal Proteins, Non-Histone, Cullin Proteins, Humans, Hypoxia-Inducible Factor 1, alpha Subunit, Kidney Neoplasms, Mice, Mutation, Missense, Neovascularization, Pathologic, Proteolysis, Transcription Factors, Ubiquitination, Von Hippel-Lindau Tumor Suppressor Protein
Amino Acid Motifs, Amino Acid Substitution, Animals, Cell Line, Chromatin, Chromosomal Proteins, Non-Histone, Cullin Proteins, Humans, Hypoxia-Inducible Factor 1, alpha Subunit, Kidney Neoplasms, Mice, Mutation, Missense, Neovascularization, Pathologic, Proteolysis, Transcription Factors, Ubiquitination, Von Hippel-Lindau Tumor Suppressor Protein
Arch. Biochem. Biophys.
Date: Feb. 15, 2012
PubMed ID: 22234250
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