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P53 family members in myogenic differentiation and rhabdomyosarcoma development

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. Keywords: oligonucleotide

ORGANISM(S): Mus musculus

PROVIDER: GSE5447 | GEO | 2006/10/16

SECONDARY ACCESSION(S): PRJNA96121

REPOSITORIES: GEO

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Transcription profiling of DeltaNp73 alpha expressing C2C12 myoblasts examined 6 and 24 hours after shifting the cells to a differentiation medium to study the functions of the individual members of P53 family.

Project description: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. Experiment Overall Design: DeltaNp73 alpha expressing C2C12 myoblasts examined 6 and 24 hours after shifting the cells to a differentiation medium.

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