Download presentation
1
von Hippel-Lindau Syndrome (VHL)
Justin Melton
2
von Hippel-Lindau Syndrome
Multi-system disorder characterized by abnormal growth of blood vessels
3
VHL the gene Tumor suppressor gene
Inherited in an Autosomal Dominant fashion Mapped to chromosome 3p25-26 using genetic linkage analysis Has 3 exons encoding 4.7 kb mRNA Highly conserved sequence in rodents and primates Homologs in C. elegans and Drosphila
4
pVHL the protein 213 amino acid protein
Has 2 main binding or active sites (alpha and beta) Alpha site binds to an E3 ligase Beta site binds to HIF-1α – a transcription factor
5
Inheritance
6
Review:
7
Normal VHL Function
8
Normal fuction important? Uh… YEAH!
9
HIF transcription factor
10
Knockout Mice Vhl-/- mice die in utero at day 10.5-12.5.
Vhl+/- are phenotypically normal and show no signs of disease until up to 15 months.
11
So what if we lose it in humans?
13
Mutations Cont.
15
VHL in Cancer
16
Future
17
Treatments? Usual cancer treatments: chemotherapy, cryotherapy, radiation and surgery. Hundreds of clinical trials currently taking place involving VHL in some fashion. Some target VHL specifically while others target downstream events, such as TGFβ transcription.
18
Sources http://www.vhl.org
Kim, William and Kaelin, William Jr. “The von Hippel-Lindau tumor suppressor protein: new insights into oxygen sensing and cancer.” Current Opinion : pp55-60. Richards, Frances. “Molecular Pathology of von Hippel-Lindau disease and the VHL tumor suppressor gene.” Exp. Rev. Mol. Med. 19 March 2001.
19
Questions?
Similar presentations
© 2025 SlidePlayer.com. Inc.
All rights reserved.