Product Pathways - Protein Stability
VHL Antibody #2738
|2738S||100 µl (10 western blots)||---||In Stock||---|
|2738||carrier free and custom formulation / quantity||email request|
|W||1:1000||Human, Mouse, Rat, Monkey||Endogenous||24||Rabbit|
Species cross-reactivity is determined by western blot.
Applications Key: W=Western Blotting
Species predicted to react based on 100% sequence homology: Bovine.
Specificity / Sensitivity
This antibody detects endogenous levels of total VHL protein (isoforms 1, 2 and 3).
Source / Purification
Polyclonal antibodies are produced by immunizing animals with a synthetic peptide corresponding to amino acids from the human VHL protein. Antibodies are purified by protein A and peptide affinity chromatography.
The Von Hippel-Lindau (VHL) protein is a substrate recognition component of an E3 ubiquitin ligase complex containing elongin BC (TCEB1 and TCEB2), cullin 1 (CUL1), and RING-box protein 1 (RBX1) (1,2,3). VHL protein has been shown to exist as three distinct isoforms resulting from alternatively spliced transcript variants (4). Loss of VHL protein function results in a dominantly inherited familial cancer syndrome that manifests as angiomas of the retina, hemangioblastomas of the central nervous system, renal clear-cell carcinomas and pheochromocytomas (4). Under normoxic conditions, VHL directs the ubiquitylation and subsequent proteosomal degradation of the hypoxia inducible factor HIF alpha, maintaining very low levels of HIF alpha in the cell. Cellular exposure to hypoxic conditions, or loss of VHL protein function, results in increased HIF alpha protein levels and increased expression of HIF-induced gene products, many of which are angiogenesis factors such as vascular endothelial growth factor (VEGF). Thus, loss of VHL protein function is believed to contribute to the formation of highly vascular neoplasias (4). In addition to HIF alpha, VHL is known to regulate the ubiquitylation of several other proteins, including tat-binding protein 1 (TBP-1), the atypical protein kinase C lambda (aPKC), and two subunits of the multiprotein RNA Polymerase II complex (RPB1 and RPB7) (5,6,7,8). Interactions with elongin BC, RPB1, RPB7 and the pVHL-associated KRAB-A domain containing protein (VHLaK) suggest that VHL may also play a more direct role in transcriptional repression.
- Kibel, A. et al. (1995) Science 269, 1444-6.
- Pause, A. et al. (1997) Proc Natl Acad Sci U S A 94, 2156-61.
- Kamura, T. et al. (2000) Proc Natl Acad Sci U S A 97, 10430-5.
- Czyzyk-Krzeska, M.F. and Meller, J. (2004) Trends Mol Med 10, 146-9.
- Corn, P.G. et al. (2003) Nat Genet 35, 229-37.
- Na, X. et al. (2003) EMBO J 22, 4249-59.
- Kuznetsova, A.V. et al. (2003) Proc Natl Acad Sci U S A 100, 2706-11.
- Li, Z. et al. (2003) EMBO J 22, 1857-67.
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This product is intended for research purposes only. The product is not intended to be used for therapeutic or diagnostic purposes in humans or animals.
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