RNF144A, an E3 ubiquitin ligase for DNA-PKcs, promotes apoptosis during DNA damage

In response to DNA damage, a proper balance between DNA repair and apoptosis is very important for genomic integrity. DNA-dependent protein kinase, catalytic subunit (DNA-PKcs) plays a key role in DNA repair. Many reports also indicate a prosurvival function for cytosolic DNA-PKcs. However, how this prosurvival activity of DNA-PKcs is regulated remains unknown. We identify Ring Finger protein 144A (RNF144A) as the first E3 ubiquitin ligase for cytosolic DNA-PKcs. RNF144A is induced in a p53-dependent manner during DNA damage and targets cytosolic DNA-PKcs for ubiquitination and degradation. The regulation of DNA-PKcs by RNF144A is important for proper apoptotic response during DNA damage, suggesting a tumor suppressor function for RNF144A.