Author/Authors :
Cam، نويسنده , , Hakan and Griesmann، نويسنده , , Heidi and Beitzinger، نويسنده , , Michaela and Hofmann، نويسنده , , Lars and Beinoraviciute-Kellner، نويسنده , , Rasa and Sauer، نويسنده , , Markus and Hüttinger-Kirchhof، نويسنده , , Nicole and Oswald، نويسنده , , Claudia and Friedl، نويسنده , , Peter and Gattenlِhner، نويسنده , , Stefan and Burek، نويسنده , , Christof and Rosenwald، نويسنده , , Andreas and Stiewe، نويسنده , , Thorsten، نويسنده ,
Abstract :
Summary
3 family comprises the tumor suppressor p53 and the structural homologs p63 and p73. How the three family members cooperate in tumor suppression remains unclear. Here, we report different but complementary functions of the individual members for regulating retinoblastoma protein (RB) function during myogenic differentiation. Whereas p53 transactivates the retinoblastoma gene, p63 and p73 induce the cyclin-dependent kinase inhibitor p57 to maintain RB in an active, hypophosphorylated state. ΔNp73 inhibits these functions of the p53 family in differentiation control, prevents myogenic differentiation, and enables cooperating oncogenes to transform myoblasts to tumorigenicity. ΔNp73 is frequently overexpressed in rhabdomyosarcoma and essential for tumor progression in vivo. These findings establish differentiation control as a key tumor suppressor activity of the p53 family.
