| First Author | Lu ZH | Year | 2005 |
| Journal | Mol Cell Biol | Volume | 25 |
| Issue | 11 | Pages | 4625-37 |
| PubMed ID | 15899865 | Mgi Jnum | J:99099 |
| Mgi Id | MGI:3581107 | Doi | 10.1128/MCB.25.11.4625-4637.2005 |
| Citation | Lu ZH, et al. (2005) YB-1 is important for late-stage embryonic development, optimal cellular stress responses, and the prevention of premature senescence. Mol Cell Biol 25(11):4625-37 |
| abstractText | Proteins containing 'cold shock' domains belong to the most evolutionarily conserved family of nucleic acid-binding proteins known among bacteria, plants, and animals. One of these proteins, YB-1, is widely expressed throughout development and has been implicated as a cell survival factor that regulates the transcription and/or translation of many cellular growth and death-related genes. For these reasons, YB-1 deficiency has been predicted to be incompatible with cell survival. However, the majority of YB-1(-/-) embryos develop normally up to embryonic day 13.5 (E13.5). After E13.5, YB-1(-/-) embryos exhibit severe growth retardation and progressive mortality, revealing a nonredundant role of YB-1 in late embryonic development. Fibroblasts derived from YB-1(-/-) embryos displayed a normal rate of protein synthesis and minimal alterations in the transcriptome and proteome but demonstrated reduced abilities to respond to oxidative, genotoxic, and oncogene-induced stresses. YB-1(-/-) cells under oxidative stress expressed high levels of the G(1)-specific CDK inhibitors p16Ink4a and p21Cip1 and senesced prematurely; this defect was corrected by knocking down CDK inhibitor levels with specific small interfering RNAs. These data suggest that YB-1 normally represses the transcription of CDK inhibitors, making it an important component of the cellular stress response signaling pathway. |
