The role of ubiquitin-proteasome pathway in oncogenic signaling.
Oncogenic activation of genes that regulate cell proliferation and survival plays a central role in the development of human cancer. This activation is frequently achieved by the aberrant expression of oncogene products due to the gene amplification, enhanced transcription or stabilization of their mRNA or protein. The ubiquitin-proteasome pathway(UPP) is the key player in the intracellular degradation of regulatory proteins in eukaryotes. UPP controls the abundance and activity of important protein regulators of cellular signal transduction including a variety of cellular proto-oncogenes. Alteration of ubiquitination and degradation of these proto-oncogene proteins often occurs during tumorigenesis and critically contributes to cell decisions as per proliferation/differentiation and survival/death. This article attempts to briefly overview the role of UPP in the regulation of several signal transduction pathways that contribute to development of cancer.
Fuchs
Serge Y
SY
Department of Animal Biology, University of Pennsylvania, School of Veterinary Medicine, Philadelphia, Pennsylvania 19104-6046, USA. sfuks@vet.upenn.edu
D002454:Cell Differentiation; D002455:Cell Division; D002470:Cell Survival; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051821:Lymphoid Enhancer-Binding Factor 1; D009097:Multienzyme Complexes / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D009369:Neoplasms / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex; D000090063:Proto-Oncogene Mas; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism; D025801:Ubiquitin / Q000378:metabolism*; D051176:beta Catenin
C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; D051821:Lymphoid Enhancer-Binding Factor 1; C000715470:MAS1 protein, human; D009097:Multienzyme Complexes; D016328:NF-kappa B; D000090063:Proto-Oncogene Mas; D012333:RNA, Messenger; D015534:Trans-Activators; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D025801:Ubiquitin; D051176:beta Catenin; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex