RRC ID 5987
著者 Miyata K, Yasukawa T, Fukuda M, Takeuchi T, Yamazaki K, Sakumi K, Tamamori-Adachi M, Ohnishi Y, Ohtsuki Y, Nakabeppu Y, Kitajima S, Onishi S, Aso T.
タイトル Induction of apoptosis and cellular senescence in mice lacking transcription elongation factor, Elongin A.
ジャーナル Cell Death Differ
Abstract 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.
巻・号 14(4)
ページ 716-26
公開日 2007-4-1
DOI 10.1038/sj.cdd.4402067
PII 4402067
PMID 17170753
MeSH Animals Apoptosis / genetics* Cellular Senescence / genetics* Elongin Female Fetal Death / genetics Fetus / abnormalities Fibroblasts / cytology Gene Expression Regulation, Developmental / genetics Immunohistochemistry Mice Mice, Inbred C57BL Mice, Knockout Pregnancy Transcription Factors / genetics* Transcriptional Elongation Factors / genetics* Transcriptional Elongation Factors / metabolism* Tumor Suppressor Protein p53 / metabolism p38 Mitogen-Activated Protein Kinases / metabolism
IF 10.717
引用数 8
WOS 分野 BIOCHEMISTRY & MOLECULAR BIOLOGY CELL BIOLOGY
リソース情報
実験動物マウス RBRC00166