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Induction of the growth inhibitor IGF-binding protein 3 by p53.

机译:p53诱导生长抑制剂IGF结合蛋白3。

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Transcriptional activation of target genes represents an important component of the tumour-suppressor function of p53 and provides a functional link between p53 and various growth-regulatory processes, including cell cycle progression (p21/WAF1), DNA repair (GADD45) and apoptosis (bax). Here we use a differential cloning approach to identify the gene encoding insulin-like growth factor binding protein 3 (IGF-BP3) as a novel p53-regulated target gene. Induction of IGF-BP3 gene expression by wild-type but not mutant p53 is associated with enhanced secretion of an active form of IGF-BP3 capable of inhibiting mitogenic signalling by the insulin-like growth factor IGF-1. Our results indicate that IGF-BP3 may link p53 to potential novel autocrine/paracrine signalling pathways and to processes regulated by or dependent on IGF(s), such as cellular growth, transformation and survival.
机译:靶基因的转录激活代表p53的肿瘤抑制功能的重要组成部分,并提供p53与各种生长调节过程之间的功能联系,包括细胞周期进程(p21 / WAF1),DNA修复(GADD45)和凋亡(bax) )。在这里,我们使用差异克隆方法来鉴定编码胰岛素样生长因子结合蛋白3(IGF-BP3)的基因为新型p53调控的靶基因。由野生型而非突变型p53诱导的IGF-BP3基因表达与能够抑制胰岛素样生长因子IGF-1的活性形式IGF-BP3的分泌增加有关。我们的结果表明,IGF-BP3可能将p53链接到潜在的新型自分泌/旁分泌信号传导途径以及受IGF调控或依赖的过程,例如细胞生长,转化和存活。

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