WB, W-S
H
Endogenous
18-22
Rabbit
#P40337
7428
Product Information
Product Usage Information
| Application | Dilution |
|---|---|
| Western Blotting | 1:1000 |
| Simple Western™ | 1:10 - 1:50 |
Storage
Specificity / Sensitivity
Species Reactivity:
Human
Source / Purification
Polyclonal antibodies are produced by immunizing animals with a synthetic peptide corresponding to residues near the carboxy terminus of human VHL protein.
Background
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) (1-3). 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 proteasomal degradation of the hypoxia-inducible factor 1α (HIF-1α), maintaining very low levels of HIF-1α in the cell. Cellular exposure to hypoxic conditions, or loss of VHL protein function, results in increased HIF-1α 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-1α, VHL is known to regulate the ubiquitylation of several other proteins, including tat-binding protein-1 (TBP-1), the atypical protein kinase C (aPKC) lambda, and two subunits of the multiprotein RNA polymerase II complex (RPB1 and RPB7) (5-8). 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.
Species Reactivity
Species reactivity is determined by testing in at least one approved application (e.g., western blot).
Western Blot Buffer
IMPORTANT: For western blots, incubate membrane with diluted primary antibody in 5% w/v BSA, 1X TBS, 0.1% Tween® 20 at 4°C with gentle shaking, overnight.
Applications Key
WB: Western Blotting W-S: Simple Western™
Cross-Reactivity Key
H: human M: mouse R: rat Hm: hamster Mk: monkey Vir: virus Mi: mink C: chicken Dm: D. melanogaster X: Xenopus Z: zebrafish B: bovine Dg: dog Pg: pig Sc: S. cerevisiae Ce: C. elegans Hr: horse GP: Guinea Pig Rab: rabbit All: all species expected
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