A novel role for cardiac ankyrin repeat protein Ankrd1/CARP as a co-activator of the p53 tumor suppressor protein.

The muscle ankyrin repeat protein family member 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/Cduanyu37 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/Cduanyu37 interacting partner and confirmed their interaction both in vivo and in vitro. We demonstrate a novel role for Ankrd1/Cduanyu37 as a transcriptional co-activator, moderately up regulating p53 activity. Furthermore, we show that p53 operates as an upstream effector of by up regulating the proximal ANKRD1 promoter. Our findings suggest that, besides acting as a transcriptional co-repressor, Ankrd1/Cduanyu37 could have a stimulatory effect on gene expression in cultured skeletal muscle cells. It is probable that Ankrd1/Cduanyu37 has a role in the propagation of signals initiated by myogenic regulatory factors (MRFs) during myogenesis.

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