Functional interaction between the transcription factor Kruppel-like factor 5 and poly(ADP-ribose) polymerase-1 in cardiovascular apoptosis
Functional interaction between the transcription factor Kruppel-like factor 5 and poly(ADP-ribose) polymerase-1 in cardiovascular apoptosis
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DOI：
10.1074/jbc.m608098200
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发表时间：
2007-03-30
影响因子：
4.8
通讯作者：
Nagai, Ryozo
中科院分区：
文献类型：
--
作者：
Suzuki, Toru;Nishi, Toshiya;Nagai, Ryozo
Kruppel样因子5（KLF 5）是一种在调节心血管对外界应激反应中起重要作用的转录因子。KLF 5调节病理性细胞生长，其乙酰化对这种作用很重要。然而，其作用机制仍不清楚。在KLF 5缺陷小鼠中的分析表明，KLF 5赋予血管病变中的凋亡抗性。机制分析进一步表明，它特异性地与聚（ADP-核糖）聚合酶-1（PARP-1）相互作用，PARP-1是一种在DNA修复和凋亡中重要的核酶。KLF 5与PARP-1的蛋白水解片段相互作用，并且在凋亡条件下KLF 5的乙酰化增加了它们的亲和力。此外，KLF 5野生型（但不是非乙酰化点突变体）抑制由PARP-1片段诱导的细胞凋亡。总的来说，我们已经发现KLF 5调节细胞凋亡和靶向PARP-1，并进一步通过乙酰化来调节这些作用。因此，我们的研究结果表明，在心血管细胞凋亡的转录因子KLF 5和PARP-1之间的功能相互作用。
Kruppel-like factor 5 (KLF5) is a transcription factor important in regulation of the cardiovascular response to external stress. KLF5 regulates pathological cell growth, and its acetylation is important for this effect. Its mechanisms of action, however, are still unclear. Analysis in KLF5-deficient mice showed that KLF5 confers apoptotic resistance in vascular lesions. Mechanistic analysis further showed that it specifically interacts with poly(ADP-ribose) polymerase-1 (PARP-1), a nuclear enzyme important in DNA repair and apoptosis. KLF5 interacted with a proteolytic fragment of PARP-1, and acetylation of KLF5 under apoptotic conditions increased their affinity. Moreover, KLF5 wild-type (but not a non-acetylatable point mutant) inhibited apoptosis as induced by the PARP-1 fragment. Collectively, we have found that KLF5 regulates apoptosis and targets PARP-1, and further, for acetylation to regulate these effects. Our findings thus implicate functional interaction between the transcription factor KLF5 and PARP-1 in cardiovascular apoptosis.