Nuclear/cytoplasmic localization of the von Hippel-Lindau tumor suppressor gene product is determined by cell density

Stephen Lee, David Y.T. Chen, Jeffrey S. Humphrey, James R. Gnarra, W. Marston Linehan, Richard D. Klausner

Research output: Contribution to journalArticle

130 Scopus citations

Abstract

The product of the von Hippel-Lindau (VHL) tumor suppressor gene, the gene inactivated in VHL disease and in sporadic clear-cell renal carcinomas, has recently been shown to have as a functional target the transcription elongation complex, elongin (also called SIII). Here it is shown that there is a tightly regulated, cell-density-dependent transport of VHL into and/or out of the nucleus. In densely grown cells, the VHL protein is predominantly in the cytoplasm, whereas in sparse cultures, most of the protein can be detected in the nucleus. We have identified a putative nuclear localization signal in the first 60 and first 28 amino acids of the human and rat VHL protein, respectively. Sequences in the C-terminal region of the VHL protein may also be required for localization to the cytosol. These findings provide the initial indication of a novel cell density-dependent pathway that is responsible for the regulation of VHL cellular localization.

Original languageEnglish (US)
Pages (from-to)1770-1775
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume93
Issue number5
DOIs
StatePublished - Mar 5 1996

ASJC Scopus subject areas

  • General

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