RRC ID 38861
Author Tsuchiya H, Iseda T, Hino O.
Title Identification of a novel protein (VBP-1) binding to the von Hippel-Lindau (VHL) tumor suppressor gene product.
Journal Cancer Res
Abstract The tumor suppressor VHL gene product (pVHL), recently reported to bind to elongins B and C, is thought to regulate transcription elongation. To establish whether the VHL gene may have other functions, we here searched for additional cellular protein(s) that might bind to pVHL using a two-hybrid system and identified seven independent clones, including elongin C, but not elongin B. Three clones (unknown, imidopeptidase, and unknown) presumably bind to the N-terminal nonconserved region, whereas the four other clones [elongin C, the HIV tat-binding protein, the actin-binding protein Filamin (ABP280), and the HIBBJ46 (named VBP-1)] were found to bind to the wild-type pVHL but not to a C-terminal 156-amino acid deletion mutant. Interestingly, the HIV tat-binding protein and Filamin could bind to C-terminal 26-amino acid deleted pVHL, but elongin C and VBP-1 failed to do so. Thus, elongin C and VBP-1 require the C-terminal end of pVHL for binding. It was also established that epitope-tagged pVHL strongly forms complexes with VBP-1 in vivo using immunoprecipitation Western blotting analysis. VBP-1 was widely expressed in various cell lines tested, in which VHL mRNA can be detected. When the VBP-1 protein was solely expressed, it located to the cytoplasm and did not localize to the nucleus. However, when coexpressed with VHL, it can translocate to the nucleus. These results indicate that VBP-1 can form a complex with VHL protein in vivo and hence VHL affects the intracellular localization of VBP-1 protein.
Volume 56(13)
Pages 2881-5
Published 1996-7-1
PMID 8674032
MeSH Amino Acid Sequence Animals Avian Proteins* Base Sequence Basic-Leucine Zipper Transcription Factors Blotting, Western Carrier Proteins / biosynthesis Carrier Proteins / genetics Carrier Proteins / metabolism* Cell Nucleus / metabolism Cytoplasm / metabolism Cytoskeletal Proteins Genes, Tumor Suppressor HeLa Cells Humans Hybrid Cells Ligases* Molecular Chaperones Molecular Sequence Data Precipitin Tests Proteins / isolation & purification Proteins / metabolism* RNA, Neoplasm / genetics RNA, Neoplasm / metabolism Transcription Factors / biosynthesis Transcription Factors / genetics Transcription Factors / metabolism* Translocation, Genetic Tumor Suppressor Proteins* Ubiquitin-Protein Ligases* Von Hippel-Lindau Tumor Suppressor Protein
IF 9.727
Times Cited 91
Human and Animal Cells COS-7(RCB0539)