title: The Role of Sumoylation in Senescence.
abstract: Cellular senescence is a program initiated by many stress signals including aberrant activation of oncogenes, DNA damage, oxidative lesions and telomere attrition. Once engaged senescence irreversibly limits cellular proliferation and potently prevents tumor formation in vivo. The precise mechanisms driving the onset of senescence are still not completely defined, although the pRb and p53 tumor suppressor pathways converge with the SUMO cascade to regulate cellular senescence. Sumoylation translocates p53 to PML nuclear bodies where it can co-operate with many sumoylated co-factors in a program that activates pRb and favors senescence. Once activated pRb integrates various proteins, many of them sumoylated, into a repressor complex that inhibits the transcription of proliferation-promoting genes and initiates chromatin condensation. Sumoylation is required for heterochromatin formation during senescence and may act as a scaffold to stabilize the pRb repressor complex. Thus, SUMO is a critical component of a tumor-suppressor network that limits aberrant cell proliferation and tumorigenesis.
authors.affiliation: Faculty of Medicine and Health Sciences, Macquarie University, NSW, Sydney, 2109, Australia.
authors.forename: Lyndee L
authors.initials: LL
authors.lastname: Scurr
authors.affiliation: UKR - Universitätsklinikum Regensburg, Klinik und Poliklinik für Dermatologie, Franz-Josef-Strauss-Allee 11, D-93053, Regensburg, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Haferkamp
authors.affiliation: Faculty of Medicine and Health Sciences, Macquarie University, NSW, Sydney, 2109, Australia. helen.rizos@mq.edu.au.
authors.forename: Helen
authors.initials: H
authors.lastname: Rizos
mesh_terms: D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism* / Q000473:pathology; D049109:Cell Proliferation; D016922:Cellular Senescence; D006801:Humans; D015398:Signal Transduction; D025841:Small Ubiquitin-Related Modifier Proteins / Q000378:metabolism*; D058207:Sumoylation; D059505:Telomere Homeostasis; D014157:Transcription Factors / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*
chemical_list: D025841:Small Ubiquitin-Related Modifier Proteins; D014157:Transcription Factors; D044767:Ubiquitin-Protein Ligases
keywords: Heterochromatin formation; PML nuclear bodies; Senescence; Telomeres; p53; pRb