The viability of vertebrate cells depends on a complex signaling interplay between survival factors and cell-death effectors. Subtle changes in the equilibrium between these regulators can result in abnormal cell proliferation or cell death, leading to various pathological manifestations. Death-associated protein kinase (DAPK) is a multidomain calcium/calmodulin (CaM)-dependent Ser/Thr protein ...

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 tra...

Metastasis is the major cause of poor prognosis in colorectal cancer (CRC), and increasing evidence supports the contribution of miRNAs to cancer progression. Here, we found that high expression of miR-103 and miR-107 (miR-103/107) was associated with metastasis potential of CRC cell lines and poor prognosis in patients with CRC. We showed that miR-103/107 targeted the known metastasis suppress...

Metastasis is themajor cause of poor prognosis in colorectal cancer (CRC), and increasing evidence supports the contribution ofmiRNAs to cancer progression. Here, we found that high expression ofmiR-103 andmiR-107 (miR-103/107) was associated with metastasis potential of CRC cell lines and poor prognosis in patients with CRC. We showed that miR-103/107 targeted the known metastasis suppressors ...

Death associated protein kinase (DAPK) is a calcium and calmodulin regulated enzyme that functions early in eukaryotic programmed cell death, or apoptosis. To validate DAPK as a potential drug discovery target for acute brain injury, the first small molecule DAPK inhibitor was synthesized and tested in vivo. A single injection of the aminopyridazine-based inhibitor administered 6 h after injury...

Aberrant promoter hypermethylation (methylation) is an epigenetic change that silences the expression of crucial genes, thus inactivating the apoptotic pathway in various cancers. Inactivation of the apoptotic pathway has been considered to be associated with chemoresistance. The objective of the present study was to clarify the effect of the methylation of the apoptosis-related genes, Bcl-2/ad...

CpG island aberrant methylation is shown to be an important mechanism in gene silencing. The important role of NF-κB in the inflammatory response to H. pylori colonization has been indicated. We investigated the influence of NFKB1 polymorphisms, -94 ins/del (rs28362491) and -449 C>G (rs72696119), on the aberrant gene methylation under H. pylori infection. Gastric mucosal samples were obtained f...

Death-associated protein kinase (DAPk) and DAPk-related protein kinase (DRP)-1 proteins are Ca+2/calmodulin-regulated Ser/Thr death kinases whose precise roles in programmed cell death are still mostly unknown. In this study, we dissected the subcellular events in which these kinases are involved during cell death. Expression of each of these DAPk subfamily members in their activated forms trig...

Death-associated protein kinase (DAPK) plays an important role in apoptosis regulation and has been shown to maintain antitumor and metastasis suppressor properties. In the present study, we investigated whether DAPK overexpression may mediate vascular endothelial growth factor (VEGF)/hypoxia-inducible factor-1α (HIF-1α) expression and angiogenic activity in the human carcinoma cell model syste...

Hyperhomocysteinemia is characterized by an abnormally high level of homocysteine (Hcy) in the blood and is associated with cardiovascular diseases such as atherosclerosis. Endothelial dysfunction may lead to the pro-atherogenic effects associated with hyperhomocysteinemia. Endothelial dysfunction induced by Hcy has been previously investigated; however, the underlying molecular mechanism remai...