title: Cellular senescence and protein degradation: breaking down cancer.
abstract: Autophagy and the ubiquitin-proteasome pathway (UPP) are the major protein degradation systems in eukaryotic cells. Whereas the former mediate a bulk nonspecific degradation, the UPP allows a rapid degradation of specific proteins. Both systems have been shown to play a role in tumorigenesis, and the interest in developing therapeutic agents inhibiting protein degradation is steadily growing. However, emerging data point to a critical role for autophagy in cellular senescence, an established tumor suppressor mechanism. Recently, a selective protein degradation process mediated by the UPP was also shown to contribute to the senescence phenotype. This process is tightly regulated by E3 ubiquitin ligases, deubiquitinases, and several post-translational modifications of target proteins. Illustrating the complexity of UPP, more than 600 human genes have been shown to encode E3 ubiquitin ligases, a number which exceeds that of the protein kinases. Nevertheless, our knowledge of proteasome-dependent protein degradation as a regulated process in cellular contexts such as cancer and senescence remains very limited. Here we discuss the implications of protein degradation in senescence and attempt to relate this function to the protein degradation pattern observed in cancer cells.
authors.affiliation: Department of Biochemistry and Molecular Medicine; Université de Montréal; Montréal, Québec, Canada.
authors.forename: Xavier
authors.initials: X
authors.lastname: Deschênes-Simard
authors.affiliation: Department of Biochemistry and Molecular Medicine; Université de Montréal; Montréal, Québec, Canada.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Lessard
authors.affiliation: Department of Biochemistry and Molecular Medicine; Université de Montréal; Montréal, Québec, Canada.
authors.forename: Marie-France
authors.initials: MF
authors.lastname: Gaumont-Leclerc
authors.affiliation: Massachusetts General Hospital Cancer Center; Harvard Medical School; Boston, MA USA.
authors.forename: Nabeel
authors.initials: N
authors.lastname: Bardeesy
authors.affiliation: Department of Biochemistry and Molecular Medicine; Université de Montréal; Montréal, Québec, Canada.
authors.forename: Gerardo
authors.initials: G
authors.lastname: Ferbeyre
mesh_terms: D001343:Autophagy; D059447:Cell Cycle Checkpoints; D002466:Cell Nucleolus / Q000378:metabolism; D016922:Cellular Senescence; D004249:DNA Damage; D006801:Humans; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology*; D059748:Proteolysis; D020543:Proteome / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012270:Ribosomes / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism
chemical_list: D020543:Proteome; D012333:RNA, Messenger; D044767:Ubiquitin-Protein Ligases
keywords: E3 ligases; ERK kinases; Ras oncogene; SASP; ubiquitin