| First Author | Yosef R | Year | 2017 |
| Journal | EMBO J | Volume | 36 |
| Issue | 15 | Pages | 2280-2295 |
| PubMed ID | 28607003 | Mgi Jnum | J:244905 |
| Mgi Id | MGI:5913684 | Doi | 10.15252/embj.201695553 |
| Citation | Yosef R, et al. (2017) p21 maintains senescent cell viability under persistent DNA damage response by restraining JNK and caspase signaling. EMBO J 36(15):2280-2295 |
| abstractText | Cellular senescence is a permanent state of cell cycle arrest that protects the organism from tumorigenesis and regulates tissue integrity upon damage and during tissue remodeling. However, accumulation of senescent cells in tissues during aging contributes to age-related pathologies. A deeper understanding of the mechanisms regulating the viability of senescent cells is therefore required. Here, we show that the CDK inhibitor p21 (CDKN1A) maintains the viability of DNA damage-induced senescent cells. Upon p21 knockdown, senescent cells acquired multiple DNA lesions that activated ataxia telangiectasia mutated (ATM) and nuclear factor (NF)-kappaB kinase, leading to decreased cell survival. NF-kappaB activation induced TNF-alpha secretion and JNK activation to mediate death of senescent cells in a caspase- and JNK-dependent manner. Notably, p21 knockout in mice eliminated liver senescent stellate cells and alleviated liver fibrosis and collagen production. These findings define a novel pathway that regulates senescent cell viability and fibrosis. |
