Transcriptional repression by RB-E2F and regulation of anchorage-independent survival.

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摘要：

Mutations that lead to anchorage-independent survival are a hallmark of . Adhesion of integrin receptors to activates a survival pathway in epithelial where phosphorylates and blocks the activity of proapoptotic such as the family member Bad, the forkhead transcription factor FKHRL-1, and . 1 () is a well-established epithelial survival factor that also triggers activation of and can maintain activity after lose matrix contact. It is not until expression diminishes (~16 h after loss of matrix contact) that epithelial deprived of matrix contact undergo apoptosis. This suggests that expression is linked to and that it is the loss of which dictates the onset of apoptosis after lose matrix contact. Here, we examine the linkage between and expression. While is able to maintain activity and of proapoptotic in that have lost matrix contact, is not able to phosphorylate and inactivate another of its substrates, (), under these conditions. The reason for this appears to be a rapid translocation of active away from when lose matrix contact. One target of is , which is turned over in response to this . Therefore, is rapidly lost when are deprived of matrix contact, leading to a loss of activity and accumulation of hypophosphorylated, active Rb. This facilitates assembly of a repressor complex containing deacetylase (HDAC), Rb, and E2F that blocks transcription of the gene for , leading to loss of activity, accumulation of active proapoptotic , and apoptosis. This feedback loop containing , , HDAC-Rb-E2F, and then determines how long will remain active after lose matrix contact, and thus it serves to regulate the onset of apoptosis in such .

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关键词：

Epithelial Cells Retinoblastoma Protein Transcription Factors transcription factor E2F 上皮细胞视网膜母细胞瘤蛋白质转录因子

DOI：

10.1128/MCB.21.10.3325-3335.2001

被引量：

137

年份：

2001