modification by NEDD8 is required for fibronectin matrix assembly and suppression of tumor development," Molecular and Cellular Biology, vol.
.--pVHL is normally expressed in benign pancreaticobiliary epithelial cells.
RACK1 causes polyubiquitination of HIF-1[alpha] by binding to Elongin C and ultimately producing Ubi-HIF-1[alpha], which is degraded by proteasomes ; RACK1-induced degradation of HIF1a is independent of oxygen, pVHL
, and PHD.
LANA, KSHV latency-associated nuclear antigen , increases the degradation of pVHL
whereas the PHDs 1 and 3 are degraded by proteasomes upon EBV infection .
VHL gene was mapped to the short arm chromosome 3 (3p25), it comprises 3 exons that encode for the 2 isoforms of the pVHL
The normal function of the VHL gene product (pVHL
) is destroying hypoxia-inducible factors (HIFa) inside cells.
It is well-established that VHL (pVHL
) regulates the protein stability of the transcription factor Hypoxia-Inducible Factor (HIF)-1 alpha through proteolysis.
Structural basis for the recognition of hydroxyproline in HIF-1 alpha by pVHL
. Nature 417:975-978.
This gene product, pVHL
, functions as a tumor suppressor protein.
Additional immunomarkers also revealed the tumor cells to be reactive to [alpha]-methylacylCoA racemase (P504S), patchy for von Hippel-Lindau tumor suppressor (pVHL
), and focally weak for carbonic anhydrase IX (CAIX).
cannot interact with HIF-1[alpha], and finally the monomer remains in the cytoplasm and migrates to the nucleus, binding to constantly expressed [beta]-monomer and forming the HIF-1[alpha] transcription factor .
En normoxia tisular, la HIF-[alfa] sufre hidroxilacion por la PHD-2 y por la FIT-1; luego, la proteina de von Hippel-Lindau (pVHL
) reconoce a este complejo hidroxilado y lo marca para su degradacion por el proteosoma.