Japan Society for the Promotion of Science:Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
Date (from‐to) : 2012/04 -2015/03
Author : SUGIMOTO Masataka
Upon stress, cells undergo irreversible growth arrest called cellular senescence. Cellular senescence acts as potent anti-tumor barrier, and recent observations suggest it is also involved in aging-associated disorders. Numerous studies have been performed to elucidate the mechanisms regulating senescence, but little is known about how post-transcriptional regulation contributes to it. In this study, we focused on the role of HuR in cellular senescence.
HuR level declined during cellular senescence. HuR knockdown induced senescence with concomitant expression of ARF protein. In addition, these cells show several senescence-associated features including the induction of cytokine induction. Moreover, adipose-specific deletion of HuR gene induced senescence in early age, which is accompanied by reduced insulin sensitivity. Together, these findings demonstrate HuR-mediated post-transcriptional regulation plays essential roles in the induction and maintenance of senescence phenotypes.