title: 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.
authors.affiliation: Molecular Tumor Biology Group, Rudolf-Virchow-Center, DFG Research Center for Experimental Biomedicine, University of Würzburg, 97078 Würzburg, Germany.
authors.forename: Hakan
authors.initials: H
authors.lastname: Cam
authors.forename: Heidi
authors.initials: H
authors.lastname: Griesmann
authors.forename: Michaela
authors.initials: M
authors.lastname: Beitzinger
authors.forename: Lars
authors.initials: L
authors.lastname: Hofmann
authors.forename: Rasa
authors.initials: R
authors.lastname: Beinoraviciute-Kellner
authors.forename: Markus
authors.initials: M
authors.lastname: Sauer
authors.forename: Nicole
authors.initials: N
authors.lastname: Hüttinger-Kirchhof
authors.forename: Claudia
authors.initials: C
authors.lastname: Oswald
authors.forename: Peter
authors.initials: P
authors.lastname: Friedl
authors.forename: Stefan
authors.initials: S
authors.lastname: Gattenlöhner
authors.forename: Christof
authors.initials: C
authors.lastname: Burek
authors.forename: Andreas
authors.initials: A
authors.lastname: Rosenwald
authors.forename: Thorsten
authors.initials: T
authors.lastname: Stiewe
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics*; D002460:Cell Line; D015972:Gene Expression Regulation, Neoplastic; D016158:Genes, p53; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008819:Mice, Nude; D018482:Muscle, Skeletal / Q000166:cytology* / Q000502:physiology*; D020411:Oligonucleotide Array Sequence Analysis; D012208:Rhabdomyosarcoma / Q000235:genetics* / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000032:analysis; D023041:Xenograft Model Antitumor Assays
chemical_list: D016159:Tumor Suppressor Protein p53