p53 family members in myogenic differentiation and rhabdomyosarcoma development - PubMed (original) (raw)

doi: 10.1016/j.ccr.2006.08.024.

Heidi Griesmann, Michaela Beitzinger, Lars Hofmann, Rasa Beinoraviciute-Kellner, Markus Sauer, Nicole Hüttinger-Kirchhof, Claudia Oswald, Peter Friedl, Stefan Gattenlöhner, Christof Burek, Andreas Rosenwald, Thorsten Stiewe

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p53 family members in myogenic differentiation and rhabdomyosarcoma development

Hakan Cam et al. Cancer Cell. 2006 Oct.

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Abstract

The p53 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. DeltaNp73 inhibits these functions of the p53 family in differentiation control, prevents myogenic differentiation, and enables cooperating oncogenes to transform myoblasts to tumorigenicity. DeltaNp73 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.

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