The Role of Mammalian STK38 in DNA Damage Response and Targeting for Radio-Sensitization

SIMPLE SUMMARY: DNA is constantly damaged by internal or external factors. Cells have evolved elaborate damage response mechanisms, namely, DNA damage response (DDR), to preserve genomic integrity. In eukaryotes, kinases play a central role in the DDR. Through a phosphorylation-dependent pathway, these mechanisms quickly transmit a DNA damage signal to the cell cycle checkpoint, cell death, or DNA-repair machinery. Recently, the role of Serine-threonine kinase 38 (STK38) in DNA-damage signaling is emerging. Here, we aim to provide an overview of current topics of STK38 in common mechanisms of regulation, DNA damage signaling, cross-talk between the DDR pathways, cancer, and the potential application for radiotherapy. ABSTRACT: Protein kinases, found in the nucleus and cytoplasm, play essential roles in a multitude of cellular processes, including cell division, proliferation, apoptosis, and signal transduction. STK38 is a member of the protein kinase A (PKA)/PKG/PKC family implicated in regulating cell division and morphogenesis in yeast and C. elegans. However, its function remained largely unknown in mammals. In recent years, advances in research on STK38 and the identification of its substrates has led to a better understanding of its function and role in mammals. This review discusses the structure, expression, and regulation of activity as a kinase, its role in the DNA damage response, cross-talk with other signaling pathways, and its application for radio-sensitization.