Von Hippel-Lindau tumor suppressor

Revision as of 15:54, 6 September 2012 by WikiBot (talk | contribs) (Robot: Automated text replacement (-{{reflist}} +{{reflist|2}}, -<references /> +{{reflist|2}}, -{{WikiDoc Cardiology Network Infobox}} +))
(diff) ← Older revision | Latest revision (diff) | Newer revision → (diff)
Jump to navigation Jump to search


Von Hippel-Lindau tumor suppressor
PDB rendering based on 1lm8.
Identifiers
Symbols VHL ; HRCA1; RCA1; VHL1
External IDs Template:OMIM5 Template:MGI HomoloGene465
RNA expression pattern
File:PBB GE VHL 203844 at tn.png
More reference expression data
Orthologs
Template:GNF Ortholog box
Species Human Mouse
Entrez n/a n/a
Ensembl n/a n/a
UniProt n/a n/a
RefSeq (mRNA) n/a n/a
RefSeq (protein) n/a n/a
Location (UCSC) n/a n/a
PubMed search n/a n/a

WikiDoc Resources for Von Hippel-Lindau tumor suppressor

Articles

Most recent articles on Von Hippel-Lindau tumor suppressor

Most cited articles on Von Hippel-Lindau tumor suppressor

Review articles on Von Hippel-Lindau tumor suppressor

Articles on Von Hippel-Lindau tumor suppressor in N Eng J Med, Lancet, BMJ

Media

Powerpoint slides on Von Hippel-Lindau tumor suppressor

Images of Von Hippel-Lindau tumor suppressor

Photos of Von Hippel-Lindau tumor suppressor

Podcasts & MP3s on Von Hippel-Lindau tumor suppressor

Videos on Von Hippel-Lindau tumor suppressor

Evidence Based Medicine

Cochrane Collaboration on Von Hippel-Lindau tumor suppressor

Bandolier on Von Hippel-Lindau tumor suppressor

TRIP on Von Hippel-Lindau tumor suppressor

Clinical Trials

Ongoing Trials on Von Hippel-Lindau tumor suppressor at Clinical Trials.gov

Trial results on Von Hippel-Lindau tumor suppressor

Clinical Trials on Von Hippel-Lindau tumor suppressor at Google

Guidelines / Policies / Govt

US National Guidelines Clearinghouse on Von Hippel-Lindau tumor suppressor

NICE Guidance on Von Hippel-Lindau tumor suppressor

NHS PRODIGY Guidance

FDA on Von Hippel-Lindau tumor suppressor

CDC on Von Hippel-Lindau tumor suppressor

Books

Books on Von Hippel-Lindau tumor suppressor

News

Von Hippel-Lindau tumor suppressor in the news

Be alerted to news on Von Hippel-Lindau tumor suppressor

News trends on Von Hippel-Lindau tumor suppressor

Commentary

Blogs on Von Hippel-Lindau tumor suppressor

Definitions

Definitions of Von Hippel-Lindau tumor suppressor

Patient Resources / Community

Patient resources on Von Hippel-Lindau tumor suppressor

Discussion groups on Von Hippel-Lindau tumor suppressor

Patient Handouts on Von Hippel-Lindau tumor suppressor

Directions to Hospitals Treating Von Hippel-Lindau tumor suppressor

Risk calculators and risk factors for Von Hippel-Lindau tumor suppressor

Healthcare Provider Resources

Symptoms of Von Hippel-Lindau tumor suppressor

Causes & Risk Factors for Von Hippel-Lindau tumor suppressor

Diagnostic studies for Von Hippel-Lindau tumor suppressor

Treatment of Von Hippel-Lindau tumor suppressor

Continuing Medical Education (CME)

CME Programs on Von Hippel-Lindau tumor suppressor

International

Von Hippel-Lindau tumor suppressor en Espanol

Von Hippel-Lindau tumor suppressor en Francais

Business

Von Hippel-Lindau tumor suppressor in the Marketplace

Patents on Von Hippel-Lindau tumor suppressor

Experimental / Informatics

List of terms related to Von Hippel-Lindau tumor suppressor


Overview

The Von Hippel-Lindau tumor suppressor protein is a protein whose inactivation is associated with Von Hippel-Lindau disease.

Von Hippel-Lindau syndrome (VHL) is a dominantly inherited familial cancer syndrome predisposing to a variety of malignant and benign tumors of the eye, brain, spinal cord, kidney, pancreas, and adrenal glands. A germline mutation of this gene is the basis of familial inheritance of VHL syndrome. The protein encoded by this gene is a component of the protein complex that includes elongin B, elongin C, and cullin-2, and possesses ubiquitin ligase E3 activity. This protein is involved in the ubiquitination and degradation of hypoxia-inducible-factor (HIF), which is a transcription factor that plays a central role in the regulation of gene expression by oxygen. RNA polymerase II subunit POLR2G/RPB7 is also reported to be a target of this protein. Alternatively spliced transcript variants encoding distinct isoforms have been observed.[1]

The disease is caused by mutations of the VHL gene on the short arm of the third chromosome (3p26-p25).

Function

The resultant protein is produced in two forms, an 18 kDa and a 30 kDa protein that functions as a tumor suppressor gene. The main action of the VHL protein is thought to be its E3 ubiquitin ligase activity that results in specific target proteins being 'marked' for degradation.

The most researched of these targets is hypoxia inducible factor 1a (HIF1a), a transcription factor that induces the expression of a number of angiogenesis related factors. (However, VHL does play other roles in tumor regulation.)[2]

Pathology

It stands to reason that the loss of VHL protein activity results in an increased amount of HIF1a, and thus increased levels of angiogenic factors, including VEGF and PDGF. In turn, this leads to unregulated blood vessel growth, one of the prerequisites of a tumour.

See also

References

  1. "Entrez Gene: VHL von Hippel-Lindau tumor suppressor".
  2. Czyzyk-Krzeska MF, Meller J (2004). "von Hippel-Lindau tumor suppressor: not only HIF's executioner". Trends in molecular medicine. 10 (4): 146–9. PMID 15162797.

Further reading

  • Graff, JW; et al. (2005). "The VHL Handbook: What You Need to Know about VHL". VHL Family Alliance. 12 (1): 1–56.
  • Lonser RR (2003). "Von Hippel-Lindau Disease". Lancet. 361 (9374): 2059–2067. PMID 12814730.
  • Neumann HP, Wiestler OD (1991). "Clustering of features of von Hippel-Lindau syndrome: evidence for a complex genetic locus". Lancet. 337 (8749): 1052–4. PMID 1673491.
  • Kamura T, Conaway JW, Conaway RC (2002). "Roles of SCF and VHL ubiquitin ligases in regulation of cell growth". Prog. Mol. Subcell. Biol. 29: 1–15. PMID 11908068.
  • Kaelin WG (2002). "Molecular basis of the VHL hereditary cancer syndrome". Nat. Rev. Cancer. 2 (9): 673–82. doi:10.1038/nrc885. PMID 12209156.
  • Conaway RC, Conaway JW (2003). "The von Hippel-Lindau tumor suppressor complex and regulation of hypoxia-inducible transcription". Adv. Cancer Res. 85: 1–12. PMID 12374282.
  • Czyzyk-Krzeska MF, Meller J (2004). "von Hippel-Lindau tumor suppressor: not only HIF's executioner". Trends in molecular medicine. 10 (4): 146–9. PMID 15162797.
  • Kaelin WG (2004). "The von Hippel-Lindau tumor suppressor gene and kidney cancer". Clin. Cancer Res. 10 (18 Pt 2): 6290S–5S. doi:10.1158/1078-0432.CCR-sup-040025. PMID 15448019.
  • Kralovics R, Skoda RC (2005). "Molecular pathogenesis of Philadelphia chromosome negative myeloproliferative disorders". Blood Rev. 19 (1): 1–13. doi:10.1016/j.blre.2004.02.002. PMID 15572213.
  • Schipani E (2006). "Hypoxia and HIF-1 alpha in chondrogenesis". Semin. Cell Dev. Biol. 16 (4–5): 539–46. doi:10.1016/j.semcdb.2005.03.003. PMID 16144691.
  • Russell RC, Ohh M (2007). "The role of VHL in the regulation of E-cadherin: a new connection in an old pathway". Cell Cycle. 6 (1): 56–9. PMID 17245122.
  • Kaelin WG (2007). "The von Hippel-Lindau tumor suppressor protein and clear cell renal carcinoma". Clin. Cancer Res. 13 (2 Pt 2): 680s–684s. doi:10.1158/1078-0432.CCR-06-1865. PMID 17255293.

External links

  • Von+Hippel-Lindau+Tumor+Suppressor+Protein at the US National Library of Medicine Medical Subject Headings (MeSH)
  • Esteban M, Harten S, Tran M, Maxwell P (2006). "Formation of primary cilia in the renal epithelium is regulated by the von hippel-lindau tumor suppressor protein". J Am Soc Nephrol. 17 (7): 1801–6. PMID 16775032.
  • Takahashi K, Iida K, Okimura Y, Takahashi Y, Naito J, Nishikawa S, Kadowaki S, Iguchi G, Kaji H, Chihara K (2006). "A novel mutation in the von Hippel-Lindau tumor suppressor gene identified in a Japanese family with pheochromocytoma and hepatic hemangioma". Intern Med. 45 (5): 265–9. PMID 16595991.
  • Hoebeeck J, Vandesompele J, Nilsson H, De Preter K, Van Roy N, De Smet E, Yigit N, De Paepe A, Laureys G, Påhlman S, Speleman F (2006). "The von Hippel-Lindau tumor suppressor gene expression level has prognostic value in neuroblastoma". Int J Cancer. 119 (3): 624–9. PMID 16506218.

Template:WH Template:WikiDoc Sources