Nuclear/cytoplasmic localization of the von Hippel-Lindau tumor suppressor gene product is determined by cell density.
S Lee, DY Chen, JS Humphrey… - Proceedings of the …, 1996 - National Acad Sciences
S Lee, DY Chen, JS Humphrey, JR Gnarra, WM Linehan, RD Klausner
Proceedings of the National Academy of Sciences, 1996•National Acad SciencesThe 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 …
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 …
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.
National Acad Sciences
