Nuclear / Cytoplasmic Localization of the Von Hippel-Lindau Tumor Suppressor Gene Product is Determined by Cell Density

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...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 1996-03, Vol.93 (5), p.1770-1775
Main Authors: Lee, Stephen, David Y. T. Chen, Humphrey, Jeffrey S., Gnarra, James R., Linehan, W. Marston, Klausner, Richard D.
Format: Article
Language:English
Subjects:
3T3 Cells
Amino Acid Sequence
Animals
Cell Compartmentation
Cell growth
Cell Line
Cell lines
Cell nucleus
Cell Nucleus - metabolism
Cells
Cellular biology
Cellular immunity
Cercopithecus aethiops
COS cells
Cytoplasm - metabolism
Exons
Fluorescent Antibody Technique, Indirect
Fluorescent antibody techniques
Genes
Ligases
Medical research
Mice
Molecular Sequence Data
Proteins
Proteins - metabolism
Rats
Tumor Suppressor Proteins
Ubiquitin-Protein Ligases
von Hippel-Lindau Disease - physiopathology
Von Hippel-Lindau Tumor Suppressor Protein
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Summary: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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.93.5.1770