The Role of Death-Associated Protein Kinase-1 in Cell Homeostasis-Related Processes

Abstract

Tremendous amount of financial resources and manpower have been invested to understand the function of numerous genes that are deregulated during the carcinogenesis process, which can be targeted for anticancer therapeutic interventions. Death-associated protein kinase 1 (DAPK-1) is one of the genes that have shown potential as biomarkers for cancer treatment. It is a member of the kinase family, which also includes Death-associated protein kinase 2 (DAPK-2), Death-associated protein kinase 3 (DAPK-3), Death-associated protein kinase-related apoptosis-inducing kinase 1 (DRAK-1) and Death-associated protein kinase-related apoptosis-inducing kinase 2 (DRAK-2). DAPK-1 is a tumour-suppressor gene that is hypermethylated in most human cancers. Additionally, DAPK-1 regulates a number of cellular processes, including apoptosis, autophagy and the cell cycle. The molecular basis by which DAPK-1 induces these cell homeostasis-related processes for cancer prevention is less understood; hence, they need to be investigated. The purpose of this review is to discuss the current understanding of the mechanisms of DAPK-1 in cell homeostasis-related processes, especially apoptosis, autophagy and the cell cycle. It also explores how the expression of DAPK-1 affects carcinogenesis. Since deregulation of DAPK-1 is implicated in the pathogenesis of cancer, altering DAPK-1 expression or activity may be a promising therapeutic strategy against cancer.

Exploring the DNA Methylation Profile of Genes Associated with Bladder Cancer in Bladder Tissue of Patients with Neurogenic Lower Urinary Tract Dysfunction

“…RARβ, in response to retinoic acid binding, can activate or repress the expression of target genes involved in various cellular processes, including cell cycle regulation, cell differentiation, proliferation, and apoptosis [ 19 ]. The DAPK gene, which encodes a serine/threonine kinase, is an inducer of cell death in response to different stimuli, including stress, DNA damage, and cytokines [ 20 ]. APC is essential in modulating cell growth and division, primarily by controlling the Wnt signaling pathway [ 21 ].…”

Investigation of the Vascular-Endothelial Pattern of Expression of DAPK-1 in Oral Squamous Cell Carcinoma and Oral Potentially Malignant Disorders Through Immunohistochemistry

“…DAPK-1 suppression has an impact on apoptosis, which, in turn, contributes to the genesis and progression of cancer. Cells lacking DAPK-1 expression as a result of promoter hypermethylation exhibit increased invasiveness and metastatic potential [ 1 ]. There is not always a direct relationship between the methylation status and expression of the DAPK-1 gene.…”

“…DAPK-1 was initially identified as a facilitator of cell death [ 1 ]. Prior research demonstrated that the downregulation of DAPK-1 expression effectively inhibited γ interferon-induced apoptotic cell death in HeLa cells (immortalized cell line).…”

“…This process enhances the functionality and variety of the proteome. DAPK-1 has both pro-apoptotic and anti-apoptotic properties [ 1 , 13 ] and a connection has been established between the expression of DAPK-1 and Fas-mediated apoptosis (Fas is a membrane protein belonging to the death receptor family. Cross-linking of Fas by its ligand, FasL, or agonistic anti-Fas antibodies, induces apoptosis of cells expressing Fas on the membrane by triggering a cascade of caspases) in human endometrial adenocarcinoma cells, shedding light on the role of DAPK-1 in promoting the survival of tumor cells [ 1 ].…”