An Overview of DAPK
Death-associated protein kinase (DAPK) is the member of a family of calmodulin (CaM) -regulated serine/threonine kinases that functions as a positive mediator of apoptosis. Apoptosis is one of the most effective methods for tumor therapeutics. It is closely related to the initiation, progression and metastasis of tumors. DAPK is a tumor suppressor involved in diverse apoptosis pathways, and it is involved in apoptosis induced by multiple pathways and is considered to be a tumor suppressor gene. Besides, DAPK can regulate or execute cell death through a variety of stimuli, including activation of death receptors, activation of cytokines, matrix desorption, and neuromycination.
The Major Types of DAPK
The DAPK family has five members: DAPK, DRP1/DAPK2 (dynamin-related protein 1 /death-associated protein kinase 2), DLK/ZIPK (DAP-like kinase /zipper interacting protein kinase), DRAK1 and DRAK2 (Death-associated protein kinase related apoptosis-inducing protein kinase 1 /Death-associated protein kinase related apoptosis-inducing protein kinase 2).
The Inhibition of DAPK
Aberrant methylation of DNA is an early event of tumorigenesis, so clinical diagnosis and treatment will benefit from methylation detection. Drugs including 5-azacytidine and 5-azido-2-deoxycytidine have been approved for clinical use. 5-azacytidine is unstable and cannot be used orally, so clinical applications are limited. 1-(β-ribonitrosourea)-1, 2-Dihydroquinidine is a new demethylation drug, which is chemically stable and has been shown to significantly reduce bladder cancer tumor volume. TC-DAPK 6 is a potent ATP-competitive selective DAPK inhibitor that acts on DAPK1 and DAPK3.
DAPK and Diseases
Loss of DAPK expression is an important cause of tumor development. Before some gastric cancers deteriorated, DAPK expression was observed to be absent from the normal mucosa of the smoked patient and adjacent to the squamous cell carcinoma. The methylation status of DAPK is associated with tumor progression, increased recurrence rate and metastasis rate, and decreased survival. Loss of DAPK expression is associated with pituitary tumors and head and neck cancer metastases. Similarly, increased tumor size, pathological status, and lymph node involvement are associated with DAPK in the absence of non-small cell lung cancer. In addition, DAPK-expressing hepatocellular carcinoma showed a higher rate of tumor differentiation, fewer metastases, less hepatic portal invasion, a higher apoptotic index, and a higher survival rate compared to hepatocellular carcinoma with a lack of DAPK expression.
Alison, M. M., Alison, M. M., Nakagawa, R., Vukovic, M. (2010) Death-associated protein kinase (DAPK) and signal transduction: regulation in cancer. FEBS Journal, 277(1): 74-80.
Steinmann, S., Scheibe, K., Erlenbach-Wuensch, K. Neufert, C., Schneider-Stock, R. (2015) Death-associated protein kinase: A molecule with functional antagonistic duality and a potential role in inflammatory bowel disease. International journal of oncology. 47(1): 5-15