DAPk Protein Family and Cancer

The Death-Associated Protein kinase (DAPk) family contains three closely related serine/threonine kinases, named DAPk, ZIPk and DRP-1, which display a high degree of homology in their catalytic domains. The recent discovery of protein-protein interactions and kinase/substrate relationships among these family members suggests that the three kinases may form multi-protein complexes capable of transmitting apoptotic or autophagic cell death signals in response to various cellular stresses including the misregulated expression of oncogenes in pre-malignant cells. Several lines of evidence indicate that the most studied member of the family, DAPk, has tumor and metastasis suppressor properties. Here we present an overview of the data connecting the DAPk family of proteins to cell death and malignant transformation and discuss the possible involvement of the autophagic cell death-inducing capacity of DAPk in its tumor suppressor activity.