Document Detail


Subcellular localization of the von Hippel-Lindau disease gene product is cell cycle-dependent.
MedLine Citation:
PMID:  9724095     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The von Hippel-Lindau gene product (pVHL) interacts with and inhibits the cellular transcription factor elongin. However, the subcellular localization of pVHL has remained uncertain. Naturally occurring pVHL mutants which fail to interact with elongin have been described in patients with VHL disease or sporadic renal cell carcinoma (RCC). Here, we have examined the cellular expression pattern of endogenous pVHL in different RCC cell lines by immunocytochemistry and confocal microscopy. Both anti-N-terminal and anti-C-terminal pVHL antibodies were able to recognize endogenous wild-type pVHL expressed by the RCC cells studied. A C-terminal truncated VHL mutant expressed by RCC cell line A498 was detected only by the N-terminal antibody but not by the C-terminal antibody as expected. The overall staining patterns of these cell lines are similar, with a predominant nuclear speckled pattern and a moderate cytoplasmic staining in subconfluent cell cultures. Interestingly, when cells reached confluency, more prominent nuclear staining with little or no cytoplasmic expression was observed. By using double labeling with anti-VHL and anti-bromodeoxyuridine (BrdU) antibodies and cell cycle analyses, we found that in the G1/G0-phase, pVHL was localized exclusively in the nucleus associated with distinctive large subnuclear structures, whereas the majority of the cells in S-phase of the cell cycle also showed a diffuse cytoplasmic staining. Our results indicate that subcellular localization of pVHL is regulated in a cell cycle-dependent manner.
Authors:
Y Ye; S Vasavada; I Kuzmin; T Stackhouse; B Zbar; B R Williams
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  International journal of cancer. Journal international du cancer     Volume:  78     ISSN:  0020-7136     ISO Abbreviation:  Int. J. Cancer     Publication Date:  1998 Sep 
Date Detail:
Created Date:  1998-09-08     Completed Date:  1998-09-08     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0042124     Medline TA:  Int J Cancer     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  62-9     Citation Subset:  IM    
Affiliation:
Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic Foundation, OH 44195, USA.
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MeSH Terms
Descriptor/Qualifier:
Carcinoma, Renal Cell / chemistry*,  pathology
Cell Line
Cell Nucleus / chemistry*
Cytoplasm / chemistry*
Humans
Interphase*
Kidney Neoplasms / chemistry*,  pathology
Ligases*
Proteins / analysis*
RNA Splicing
Tumor Suppressor Proteins*
Ubiquitin-Protein Ligases*
Von Hippel-Lindau Tumor Suppressor Protein
von Hippel-Lindau Disease / genetics*
Grant Support
ID/Acronym/Agency:
DK47101/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Proteins; 0/Tumor Suppressor Proteins; EC 6.-/Ligases; EC 6.3.2.19/Ubiquitin-Protein Ligases; EC 6.3.2.19/VHL protein, human; EC 6.3.2.19/Von Hippel-Lindau Tumor Suppressor Protein

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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