Death-associated protein kinase 1 (DAPK1)

Death-associated protein kinase 1 (DAPK1) is a large, multidomain, calcium/calmodulin-dependent serine/threonine kinase widely recognized for its pivotal role in regulating apoptosis, autophagy, and cellular stress responses. Structurally, DAPK1 contains an N-terminal kinase domain, a calmodulin regulatory domain, eight ankyrin repeats, a ROC-COR (Ras of complex proteins with a C-terminal of ROC) domain, a death domain, and a serine-rich tail[1][2][3][5]. DAPK1 is a critical node in cell death signaling pathways, functioning as both a tumor suppressor and a mediator of neurodegeneration, and is regulated via phosphorylation, protein-protein interactions, and intracellular localization. Given its diverse roles in cancer, neurodegenerative diseases such as Alzheimer's disease and stroke, and inflammatory responses, DAPK1 has emerged as a promising but challenging therapeutic target for drug discovery, with ongoing efforts to develop selective inhibitors that minimize adverse effects on its tumor suppressor activity and other physiological functions[1][2][3][5][7].

Other names

DAPKDAP kinase 1ROCO3death-associated protein kinase 1

Inhibition of kinase catalytic activity (ATP-competitive inhibition), disruption of substrate phosphorylation, interference with autophagy and apoptotic signaling.