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

Yanlai Lai, Meihua Song, Kevin Hakala, Susan E Weintraub, Yuzuru Shiio

Research output: Contribution to journalArticle

23 Citations (Scopus)

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

Fingerprint

Dissection
Proteomics
Tumors
Protein Isoforms
Protein-Arginine N-Methyltransferases
Cullin Proteins
Neoplasms
Ubiquitin-Protein Ligases
Cilia
Ligases
Ubiquitin
Tumor Suppressor Genes
Extracellular Matrix
Biosynthesis
Carcinogenesis
Collagen
Maintenance
Genes
Enzymes
Hypoxia

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Chemistry(all)

Cite this

Proteomic dissection of the von hippel-Lindau (VHL) interactome. / Lai, Yanlai; Song, Meihua; Hakala, Kevin; Weintraub, Susan E; Shiio, Yuzuru.

In: Journal of Proteome Research, Vol. 10, No. 11, 04.11.2011, p. 5175-5182.

Research output: Contribution to journalArticle

Lai, Yanlai ; Song, Meihua ; Hakala, Kevin ; Weintraub, Susan E ; Shiio, Yuzuru. / Proteomic dissection of the von hippel-Lindau (VHL) interactome. In: Journal of Proteome Research. 2011 ; Vol. 10, No. 11. pp. 5175-5182.
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