| First Author | Miyata K | Year | 2007 |
| Journal | Cell Death Differ | Volume | 14 |
| Issue | 4 | Pages | 716-26 |
| PubMed ID | 17170753 | Mgi Jnum | J:119126 |
| Mgi Id | MGI:3701248 | Doi | 10.1038/sj.cdd.4402067 |
| Citation | Miyata K, et al. (2007) Induction of apoptosis and cellular senescence in mice lacking transcription elongation factor, Elongin A. Cell Death Differ 14(4):716-26 |
| abstractText | Elongin A is a transcription elongation factor that increases the overall rate of mRNA chain elongation by RNA polymerase II. To gain more insight into the physiological functions of Elongin A, we generated Elongin A-deficient mice. Elongin A homozygous mutant (Elongin A(-/-)) embryos demonstrated a severely retarded development and died at between days 10.5 and 12.5 of gestation, most likely due to extensive apoptosis. Moreover, mouse embryonic fibroblasts (MEFs) derived from Elongin A(-/-) embryos exhibited not only increased apoptosis but also senescence-like growth defects accompanied by the activation of p38 MAPK and p53. Knockdown of Elongin A in MEFs by RNA interference also dramatically induced the senescent phenotype. A study using inhibitors of p38 MAPK and p53 and the generation of Elongin A-deficient mice with p53-null background suggests that both the p38 MAPK and p53 pathways are responsible for the induction of senescence-like phenotypes, whereas additional signaling pathways appear to be involved in the mediation of apoptosis in Elongin A(-/-) cells. Taken together, our results suggest that Elongin A is required for the transcription of genes essential for early embryonic development and downregulation of its activity is tightly associated with cellular senescence.Cell Death and Differentiation (2007) 14, 716-726. doi:10.1038/sj.cdd.4402067; published online 15 December 2006. |
