p63 and p73 transactivate differentiation gene promoters in human keratinocytes

p53 and its two homologues, p73 and p63, share considerable structural simi larities, an ability to interact between themselves and to transactivate th e same promoters, including for example p21. Furthermore, p73 can induce ce ll death via its interaction with c-Abl, In contrast, p63 has been demonstr ated to be essential for limb and skin formation. We evaluated the expressi on of p63 and p73 in differentiating human keratinocytes in vitro. Skin bio psy and primary cultures of normal human epidermal keratinocytes (NHEK) exp ress both p73 and p63. NHEK induced to differentiate in vitro by high calci um exposure show induction of p73 delta and downregulation of all isoforms of p63. This latter gene is predominantly expressed in its transcriptionall y inactive form, Delta Np63. We further evaluated the effect of either p73s or p63 transfected in either NHEK or transformed human keratinocytes (HaCa t cells). p73 gamma, delta, and p63 were able to transactivate the promoter s of loricrin and involucrin in both NHEK and HaCat cells. These results su ggest the involvement of both p73 and p63 genes in keratinocyte terminal di fferentiation. (C) 2000 Academic Press.