Proteomic dissection of the von hippel-Lindau (VHL) interactome

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

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

The von Hippel-Lindau (VHL) tumor suppressor gene encodes a component of a ubiquitin ligase complex containing elongin B, elongin C, cullin 2, and Rbx1, which acts as a negative regulator of hypoxia inducible factor (HIF). VHL ubiquitinates and degrades the alpha subunits of HIF, and this is proposed to suppress tumorigenesis and tumor angiogenesis. Several lines of evidence also suggest important roles for HIF-independent VHL functions in the maintenance of primary cilium, extracellular matrix formation, and tumor suppression. We undertook a series of proteomic analyses to gain a comprehensive picture of the VHL-interacting proteins. We found that the ARF tumor suppressor interacts with VHL30, a longer VHL isoform, but not with VHL19, a shorter VHL isoform. ARF was found to release VHL30 from the E3 ligase complex, promoting the binding of VHL30 to a protein arginine methyltransferase, PRMT3. Our analysis of the VHL19 interactome also uncovered that VHL19 displays an affinity to collagens and their biosynthesis enzymes.

Original languageEnglish (US)
Pages (from-to)5175-5182
Number of pages8
JournalJournal of Proteome Research
Volume10
Issue number11
DOIs
StatePublished - Nov 4 2011

Keywords

  • ARF
  • PRMT3
  • interactome
  • p53
  • proteomics
  • von Hippel-Lindau tumor suppressor

ASJC Scopus subject areas

  • Biochemistry
  • Chemistry(all)

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