In colon cancer cells, hypoxia also reduces TP53 function by promoting inhibitory alternative HDAC6 intron-retention splicing, de-regulating the unfolded protein response (UPR), protein aggregate processing, altering the cell response to cytotoxic stress, reducing HDAC6-dependent TP53 binding protein-1 expression, repressing expression of the p53 target gene P21/Waf1 cell cycle inhibitor and impairing recognition of H4K20me2 and H2AK15ub histone marks induced by DNA double strand breaks and DNA repair [118]. The gene discussed is HDAC6; the disease is malignant colon neoplasm.