Role of the ubiquitin proteasome system in renal cell carcinoma.
Renal cell carcinoma (RCC) accounts for approximately 2.6% of all cancers in the United States. While early stage disease is curable by surgery, the median survival of metastatic disease is only 13 months. In the last decade, there has been considerable progress in understanding the genetics of RCC. The VHL tumor suppressor gene is inactivated in the majority of RCC cases. The VHL protein (pVHL) acts as an E3 ligase that targets HIF-1, the hypoxia inducible transcription factor, for degradation by the ubiquitin proteasome system (UPS). In RCC cases with mutant pVHL, HIF-1 is stabilized and aberrantly expressed in normoxia, leading to the activation of pro-survival genes such as vascular endothelial growth factor (VEGF). This review will focus on the defect in the UPS that underlies RCC and describe the development of novel therapies that target the UPS. Publication history: Republished from Current BioData's Targeted Proteins database (TPdb; http://www.targetedproteinsdb.com).
Corn
Paul G
PG
MD Anderson Cancer Center, GU Medical Oncology, Box 1374, 1515 Holcombe Boulevard, Houston, TX 77030, USA. pcorn@mdanderson.org
D000818:Animals; D002292:Carcinoma, Renal Cell / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics; D046988:Proteasome Endopeptidase Complex / Q000502:physiology*; D061988:Proteasome Inhibitors; D043743:Ubiquitin-Protein Ligase Complexes / Q000037:antagonists & inhibitors / Q000502:physiology*
D004791:Enzyme Inhibitors; D061988:Proteasome Inhibitors; D043743:Ubiquitin-Protein Ligase Complexes; D046988:Proteasome Endopeptidase Complex