Von Hippel Lindau Binding protein 1
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The Von Hippel Lindau Binding protein 1 is a heterohexameric chaperone protein of two PFD-alpha type and four PFD-beta type subunits based on its ability to capture unfolded actin. It binds specifically to cytosolic chaperonin (c-cpn) and transfers target proteins to it [1]. The name hippel lindau binding protein 1 is a synonym for the name Prefoldin subunit 3 and it belongs to the prefoldin alpha subunit family. The Human von hippel lindau binding protein is cytoplasmic, nuclear, and membrane- associated. Isoform 1 of this protein is found predominantly in the cytoplasm and is with less amounts nuclear or membrane-associated. Isoform 3 is equally distributed between the nucleus and the cytoplasm but is not membrane-associated. In complex with VHL, it can translocate to the nucleus.
This protein plays a role in the transport of the Von Hippel-Lindau protein from the perinuclear granules to the nucleus or cytoplasm [2]. It transfers target proteins to cytosolic chaperonin (C-CPN), promotes folding of nascent polypeptide chain in an environment in which there are many competing pathways for nonnative protein. The pathway in which the VBP1 mediates is the ubiquitin proteolysis. Complexing with VHL to form an intracellular complex
The Von hippel lindau gene encodes a tumor suppressor protein. It complexes with CUL2, elongin B, elongin C Rbx/ROC1 and an ubiquitin conjugating enzyme other than CDC34, either UBE2B, 2D1, L6 or others to form an active E3 ubiquitin ligase complex named the VCB-CUL2 complex, targeting and regulating the hypoxia inducible protein HIF in normoxic conditions. It is also involved in cell cycle regulation exit of cell cycle upon serum withdrawal and in extracellular matrix formation through interaction with fibronectin, which may be an inhibitor of the transcriptor elongation factor B (SIII) through competition to binding TCEB1 and TCEBD.
Inactivation of the VHL tumor suppressor gene is an early, causal event in the development of clear cell renal cell carcinomas and hemangioblastomas. Its protein product, pVHL, is part of an E3 ubiquitin ligase complex that targets HIF subunits for destruction in the presence of oxygen. Accordingly, pVHL-defective tumor cells overproduce a variety of HIF target genes, which have been implicated in metabolism, mitogenesis, and angiogenesis.
[3] used the murine Vbp1 cDNA to investigate the expression of the Vbp1 mRNA in the mouse by in situ hybridization and Northern blot analysis. In fetal stages between days 9 and 18 of gestation, Vbp1 was expressed mainly in the central nervous system, retina, and liver. In addition, at day 12, high expression was observed in the labyrinthine region of the placenta. In later stage placentas, Vbp1 expression was, however, considerably reduced. Northern blot analysis of adult mouse tissues showed that Vbp1 was ubiquitously expressed. In situ analysis of several adult tissues showed that in most tissues the transcripts were evenly distributed. In brain, eye, kidney, and intestine, however, Vbp1 was expressed in specific cell types. In cerebellum and various tumors of VHL patients, no consistent differences in VBP1 expression levels could be detected between tumors characteristic of von Hippel-Lindau disease and normal tissue. Mapping of the murine Vbp1 gene revealed conserved chromosomal localization between mouse and human in a region homologous to human Xq2.
