SIAH2 and breast carcinoma: In contrast, in breast cancer cells, HIPK2 is degraded during periods of low oxygen via association with the E3 ubiquitin ligase SIAH2 (Calzado et al., 2009); this degradation of HIPK2 is necessary as the protein normally represses the expression of HIF-1α by binding at its promoter (Nardinocchi et al., 2009).