INDUCTION OF THE GROWTH INHIBITOR IGF-BINDING PROTEIN-3 BY P53
INDUCTION OF THE GROWTH INHIBITOR IGF-BINDING PROTEIN-3 BY P53
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DOI：
10.1038/377646a0
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发表时间：
1995-10-19
期刊：
影响因子：
64.8
通讯作者：
KLEY, N
中科院分区：
文献类型：
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作者：
BUCKBINDER, L;TALBOTT, R;KLEY, N
靶基因的转录激活是p53肿瘤抑制功能的重要组成部分，并在p53和各种生长调节过程之间提供功能性联系，包括细胞周期进展（p21/WAF 1）（1-3）、DNA修复（GADD 45）（4）和凋亡（bax）（5）。在这里，我们使用差异克隆的方法来确定胰岛素样生长因子结合蛋白3（IGF-BP 3）作为一个新的p53调控的靶基因编码基因。野生型而非突变型p53对IGF-BP 3基因表达的诱导与IGF-BP 3活性形式的分泌增强有关，该IGF-BP 3活性形式能够抑制胰岛素样生长因子IGF-1的促有丝分裂信号传导。我们的结果表明，ICF-BP 3可能将p53与潜在的新的自分泌/旁分泌信号传导途径以及由IGF调节或依赖于IGF的过程（如细胞生长、转型与生存
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)(1-3), DNA repair (GADD45)(4) and apoptosis (bax)(5). 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 ICF-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.