Disease relevance of VBP1

• Moreover, expression of the human VBP1 gene was investigated in cerebellum and in various tumours of VHL patients encompassinghaemangioblastomas, renal cell carcinomas and pheochromocytomas [1].
• The messenger RNA (mRNA) from 5 of 69 patients with severe hemophilia A did not support amplification of complementary DNA containing the first few exons of the factor VIII (F8) gene but supported amplification of mRNA containing exon 1 of F8 plus exons of the VBP1 gene [2].

High impact information on VBP1

• In later stage placentas, Vbp1 expression was, however, considerably reduced [1].
• In fetal stages between days 9 and 18 of gestation, Vbp1 was expressed mainly in the central nervous system, retina and liver [1].
• Three-hybrid analysis suggested that VBP1 could compete with hMSH5 for the binding of hMSH4 [3].
• As a step forward to the understanding of the molecular mechanisms underlying the roles of these two mammalian MutS homologues, here we have identified von Hippel-Lindau (VHL) tumor suppressor-binding protein 1 (VBP1) as an interacting protein partner for human MSH4 (hMSH4) [3].
• Thus, elongin C and VBP-1 require the C-terminal end of pVHL for binding [4].

Biological context of VBP1

• Identification of a novel protein (VBP-1) binding to the von Hippel-Lindau (VHL) tumor suppressor gene product [4].
• VBP1 is unlike other known proteins but a consensus for tyrosine phosphorylation possibly suggests regulation by kinases [5].
• Although most of the regions in pVHL that had been implicated in binding specific proteins demonstrated evolutionary conservation, the carboxy-terminal putative VBP-1 binding site was less well conserved, suggesting that VBP-1 binding may have less functional significance [6].
• This suggests that the VBP-1 product is necessary for morphogenesis [7].
• Double-stranded RNA interference (RNAi) against VBP-1 resulted in an arrest of embryogenesis at morula stages [7].

Anatomical context of VBP1

• VBP-1 was widely expressed in various cell lines tested, in which VHL mRNA can be detected [4].

Other interactions of VBP1

• The protein encoded by hMSH4sv was unable to interact with hMSH5, but it retained the capacity to interact with VBP1 [3].
• A further VHL-binding protein of unknown function, VBP1, fails to bind to truncated forms of VHL [8].

Analytical, diagnostic and therapeutic context of VBP1

• It was also established that epitope-tagged pVHL strongly forms complexes with VBP-1 in vivo using immunoprecipitation Western blotting analysis [4].
• Northern blot analysis of adult mouse tissues showed that Vbp1 was ubiquitously expressed [1].

References