Beschreibung:
<jats:title>Significance</jats:title>
<jats:p>Activation of the cell death (apoptosis) program is a major principle of DNA-damaging cancer treatments including ionizing radiation and chemotherapeutic drug treatment. The protein kinase HIPK2 plays a key role in radiosensitivity and chemosensitivity. Here, we found that HIPK2 autointeracts and autophosphorylates after DNA damage. HIPK2 autophosphorylation is conserved in evolution and regulates its apoptosis-inducing activity by facilitating binding of the isomerase Pin1. Pin1 couples HIPK2 activation to its stabilization and is essential for DNA damage-induced apoptosis in cancer cells and in zebrafish. Our findings identify a mechanism linking HIPK2 activation to its stabilization and highlight a conserved function of HIPK2 and Pin1 in the DNA damage-induced apoptosis response.</jats:p>