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. 2007 Jan 26;128(2):295-308.
doi: 10.1016/j.cell.2006.11.050.

PRAK is essential for ras-induced senescence and tumor suppression

Peiqing Sun  1 , Naoto Yoshizuka, Liguo New, Bettina A Moser, Yilei Li, Rong Liao, Changchuan Xie, Jianming Chen, Qingdong Deng, Maria Yamout, Meng-Qiu Dong, Costas G Frangou, John R Yates 3rd, Peter E Wright, Jiahuai Han
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Free article

PRAK is essential for ras-induced senescence and tumor suppression

Peiqing Sun et al. Cell. .
Free article

Abstract

Like apoptosis, oncogene-induced senescence is a barrier to tumor development. However, relatively little is known about the signaling pathways mediating the senescence response. p38-regulated/activated protein kinase (PRAK) is a p38 MAPK substrate whose physiological functions are poorly understood. Here we describe a role for PRAK in tumor suppression by demonstrating that PRAK mediates senescence upon activation by p38 in response to oncogenic ras. PRAK deficiency in mice enhances DMBA-induced skin carcinogenesis, coinciding with compromised senescence induction. In primary cells, inactivation of PRAK prevents senescence and promotes oncogenic transformation. Furthermore, we show that PRAK activates p53 by direct phosphorylation. We propose that phosphorylation of p53 by PRAK following activation of p38 MAPK by ras plays an important role in ras-induced senescence and tumor suppression.

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