The interaction of the von Hippel-Lindau tumor suppressor and heterochromatin protein 1

Yanlai Lai, Meihua Song, Kevin Hakala, Susan T. Weintraub, Yuzuru Shiio

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

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-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.

Original languageEnglish (US)
Pages (from-to)103-110
Number of pages8
JournalArchives of Biochemistry and Biophysics
Volume518
Issue number2
DOIs
StatePublished - Feb 15 2012

Keywords

  • Heterochromatin protein 1
  • Interaction
  • Mass spectrometry
  • Renal carcinoma
  • Von Hippel-Lindau tumor suppressor

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology

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