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Repression Of The Sumo-Specific Protease Senp1 Induces P53-Dependent Premature Senescence In Normal Human Fibroblasts, Kristin E. Yates, Gregory A. Korbel, Michael Shtutman, Igor Roninson, Daniel Dimaio

Faculty Publications

The proliferative lifespan of normal somatic human cells in culture terminates in a permanent growth-arrested state known as replicative senescence. In this study, we show that RNA interference-mediated repression of the genes encoding the small ubiquitin-related modifier (SUMO)-specific proteases, Senp1, Senp2, and Senp7, induced low passage primary human fibroblasts to senesce rapidly. Following Senp1 repression, we observed a global increase in sumoylated proteins and in the number and size of nuclear SUMO-containing promyelocytic leukemia (PML) bodies. SUMO/PML bodies also increased during replicative senescence. p53 transcriptional activity was enhanced towards known p53 target genes following repression of Senp1, and inhibition of …