DNA damaging agent doxorubicin induces the expression of myotonic dystrophy kinase protein in tumor suppressor p53 dependent manner

Tumor suppressor p53 plays an integral role in DNA damage-induced apoptosis, which is one of the biological processes to protect against tumor progression. Cell shape is dramatically changed undergoing apoptosis, which is often associated with actomyosin contraction; however, it remains entirely elusive how p53 regulates actomyosin contraction in response to DNA-damaging agent. We here show that p53 controls expression of myotonic dystrophy protein kinase (DMPK), which is known to upregulate actomyosin contraction. To identify a novel p53 regulating gene encoding the modulator of myosin, we performed a DNA microarray and then found that, in response to DNA-damaging agent doxorubicin, DMPK expression was increased in a p53-dependent manner. Gene expression analysis of p53+/+ (wild-type: WT) and p53−/− mouse embryonic fibroblasts (MEFs) in the absence and presence of doxorubicin was performed using Agilent Mouse Gene Expression 4x44K v2 Microarray as one color experiments.