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

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 93; no. 5; pp. 1770 - 1775
• Main Authors: Lee, Stephen, David Y. T. Chen, Humphrey, Jeffrey S., Gnarra, James R., Linehan, W. Marston, Klausner, Richard D.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences of the United States of America 05.03.1996; National Acad Sciences; National Academy of Sciences
• 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
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.93.5.1770

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.