DEREGULATED TRANSCRIPTION FACTOR E2F-1 EXPRESSION LEADS TO S-PHASE ENTRY AND P53-MEDIATED APOPTOSIS

DEREGULATED TRANSCRIPTION FACTOR E2F-1 EXPRESSION LEADS TO S-PHASE ENTRY AND P53-MEDIATED APOPTOSIS
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DOI:
10.1073/pnas.91.23.10918
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发表时间:
1994-11-08
影响因子:
11.1
通讯作者:
ADAMS, PD
ADAMS, PD
中科院分区:
综合性期刊1区
文献类型:
--
作者:
QIN, XQ;LIVINGSTON, DM;ADAMS, PD

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E2F-1是一种转录因子,被怀疑可以激活S期所需的基因,也是视网膜母细胞瘤基因产物Rb的已知作用靶点。在静止的成纤维细胞中,它的诱导导致S期进入细胞周期,继而导致细胞凋亡。野生型Rb或突变型P53的共表达可抑制E2F-1介导的细胞凋亡。相反,在这些条件下,自然发生的功能丧失的Rb突变体或野生型P53的共表达并不抑制细胞凋亡的诱导。因此,解除调控的E2F-1活性会产生增殖和凋亡信号。P53似乎参与了后者的执行。
E2F-1 is a transcription factor suspected of activating genes required for S phase and a known target for the action of RB, the retinoblastoma gene product. Its induction in quiescent fibroblasts led to S-phase entry followed by apoptosis. E2F-1-mediated apoptosis was suppressed by coexpression of wild-type RB or a transdominant negative mutant species of p53. In contrast, coexpression of a naturally occurring loss-of-function RB mutant or wild-type p53 did not suppress the induction of apoptosis under these conditions. Thus, deregulated E2F-1 activity gives rise to proliferative and apoptotic signals. p53 appears to participate in the execution of the latter.