HIPK2 and cancer: When p53 is present, lethal DNA damage induces accumulation of HIPK2 and subsequent phosphorylation of p53 at serine 46 by HIPK2, which in turn activates apoptotic p53-target genes such as PUMA, Bax and Noxa. 9, 10 Therefore, HIPK2 has been recognized as a target for cancer therapy.