Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, 11010 Belgrade, Serbia.
Arch Biochem Biophys. 2010 Oct 1;502(1):60-7. doi: 10.1016/j.abb.2010.06.029. Epub 2010 Jul 3.
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.
肌锚蛋白重复蛋白（MARP）家族成员 Ankrd1/CARP 是肌节中肌联蛋白机械感觉信号复合物的一部分，它对拉伸有反应，易位到细胞核，作为转录共阻遏物参与心脏基因的调节。已有几项研究集中在它在肌肉中的结构作用，但它的调节作用仍知之甚少。为了更深入地了解 Ankrd1/CARP 的调节功能，我们寻找可能相互作用并调节其活性的转录因子。使用蛋白质阵列方法，我们确定肿瘤抑制蛋白 p53 是 Ankrd1/CARP 的相互作用伙伴，并在体内和体外都证实了它们的相互作用。我们证明了 Ankrd1/CARP 作为转录共激活物的新作用，适度上调 p53 活性。此外，我们还表明，p53 通过上调近端 ANKRD1 启动子，作为 Ankrd1/CARP 的上游效应物起作用。我们的发现表明，除了作为转录共阻遏物外，Ankrd1/CARP 还可能对培养的骨骼肌细胞中的基因表达产生刺激作用。Ankrd1/CARP 可能在肌发生过程中肌生成调节因子（MRFs）引发的信号传播中发挥作用。
