A novel role for cardiac ankyrin repeat protein Ankrd1/CARP as a co-activator of the p53 tumor suppressor protein
A novel role for cardiac ankyrin repeat protein Ankrd1/CARP as a co-activator of the p53 tumor suppressor protein
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DOI：
10.1016/j.abb.2010.06.029
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发表时间：
2010-10-01
影响因子：
3.9
通讯作者：
Faulkner, Georgine
中科院分区：
文献类型：
--
作者：
Kojic, Snezana;Nestorovic, Aleksandra;Faulkner, Georgine
肌锚蛋白重复序列蛋白（MARP）家族成员Ankrd 1/CARP是肌节中肌联蛋白-机械感觉信号复合物的一部分，并且响应于拉伸，它易位到细胞核，在那里它作为转录共抑制物参与心脏基因的调节。一些研究集中在它在肌肉中的结构作用，但它的调节作用仍然知之甚少。为了更深入地了解Ankrd 1/CARP的调节功能，我们寻找可以相互作用并调节其活性的转录因子。使用蛋白质阵列方法，我们鉴定了肿瘤抑制蛋白p53作为Ankrd 1/CARP相互作用伴侣，并证实了它们在体内和体外的相互作用。我们证明了Ankrd 1/CARP作为转录共激活因子的新作用，适度上调p53活性。此外，我们表明p53作为Ankrd 1/CARP的上游效应物起作用，通过上调近端ANKRD 1启动子，我们的发现提示，除了作为转录辅阻遏物，Ankrd 1/CARP可能对培养的骨骼肌细胞基因表达具有刺激作用。CARP在肌生成过程中由肌生成调节因子（MRF）启动的信号传播中发挥作用（C）2010 Elsevier Inc版权所有
The muscle ankyrin repeat protein (MARP) family member Ankrd1/CARP is a part of the titin-mechanosensory signaling complex in the sarcomere and in response to stretch it translocates to the nucleus where it participates in the regulation of cardiac genes as a transcriptional co-repressor. Several studies have focused on its structural role in muscle, but its regulatory role is still poorly understood To gain more insight into the regulatory function of Ankrd1/CARP we searched for transcription factors that could interact and modulate its activity. Using protein array methodology we identified the tumor suppressor protein p53 as an Ankrd1/CARP interacting partner and confirmed their interaction both in vivo and in vitro We demonstrate a novel role for Ankrd1/CARP as a transcriptional co-activator, moderately up regulating p53 activity Furthermore, we show that p53 operates as an upstream effector of Ankrd1/CARP, by up regulating the proximal ANKRD1 promoter Our findings suggest that, besides acting as a transcriptional co-repressor, Ankrd1/CARP could have a stimulatory effect on gene expression in cultured skeletal muscle cells It is probable that Ankrd1 /CARP has a role in the propagation of signals initiated by myogenic regulatory factors (MRFs) during myogenesis (C) 2010 Elsevier Inc All rights reserved