This study investigates the role of p73 in epidermal carcinogenesis and DNA damage responses within the context of p53 family signaling. Loss of p73 promoted malignant conversion of keratinocytes to squamous cell carcinoma and conferred resistance to ionizing radiation, effects reversible by reconstitution of TAp73α but not ΔNp73α. p73 was shown to functionally cooperate with transcriptionally active p63 isoforms to regulate cell cycle arrest and gene expression, while its tumor suppressive role was uncoupled from radiation sensitivity. These findings highlight p73 as a critical regulator of p53 family balance, tumor suppression, and treatment response.
