The ubiquitin E3 ligase RNF144A transfers ubiquitin from the E2-ubiquitin conjugate UBE2L3:Ubiquitin to an unknown residue of PRKDC (DNA-PKcs, the catalytic subunit of DNA-dependent protein kinase) (Ho et al. 2014). RNF144A polyubiquitinates PRKDC with lysine-48 linked ubiquitin, leading to proteasomal degradation of PRKDC. Expression of RNF144A is activated by TP53 (p53) and the degradation of PRKDC caused by RNF144A may be pro-apoptotic (Ho et al. 2014). RNF144A contains a transmembrane domain that localizes RNF144A to endosomal membranes (Ho et al. 2015).