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Death-associated protein kinase (DAPK) is a pro-apoptotic serine⁄threo-nine protein kinase that is dysregulated in a wide variety of cancers. The mechanism by which this occurs has largely been attributed to promoter hypermethylation, which results in gene silencing. | MINIREVIEW Death-associated protein kinase DAPK and signal transduction regulation in cancer Alison M. Michie Alison M. McCaig Rinako Nakagawa and Milica Vukovic Section of ExperimentalHaematology Division of Cancer Sciences Faculty of Medicine University of Glasgow UK Keywords cancer CpG methylation DAPK ERK-mitogen-activated protein kinase post-translationalregulation Correspondence A. M. Michie Section of Experimental Haematology Division of Cancer Sciences Faculty of Medicine University of Glasgow PaulO Gorman Leukaemia Research Centre Gartnavel General Hospital 21 Shelley Road Glasgow G12 0XB UK Fax Tel 44 141 3O1 7898 E-mail A.Michie@udcf.gla.ac.uk Received 11 March 2009 revised 28 May 2009 accepted 17 June 2009 doi 10.1111 j.1742-4658.2009.07414.x Death-associated protein kinase DAPK is a pro-apoptotic serine threo-nine protein kinase that is dysregulated in a wide variety of cancers. The mechanism by which this occurs has largely been attributed to promoter hypermethylation which results in gene silencing. However recent studies indicate that DAPK expression can be detected in some cancers but its function is still repressed suggesting that DAPK activity can be subverted at a post-translational level in cancer cells. This review will focus on recent data describing potential mechanisms that may alter the expression regulation or function of DAPK. Introduction Death-associated protein kinase DAPK is a cal-cium calmodulin-regulated serine threonine protein kinase located on chromosome 9q21.33 which is composed of several functional domains including a kinase domain an ankyrin repeat domain and a death domain 1 2 . DAPK was first identified as a mediator of interferon-y-mediated apoptosis 3 4 . Subsequently DAPK has been found to participate in a number of additional apoptosis-inducing pathways downstream of CD95 Fas tumour necrosis factor-a and transforming growth factor-b 5 6 . The death domain regulates the pro-apoptotic function of DAPK in part by .
