title: A ribosomal protein L23-nucleophosmin circuit coordinates Mizl function with cell growth.
abstract: The Myc-associated zinc-finger protein, Miz1, is a negative regulator of cell proliferation and induces expression of the cell-cycle inhibitors p15(Ink4b) and p21(Cip1). Here we identify the ribosomal protein L23 as a negative regulator of Miz1-dependent transactivation. L23 exerts this function by retaining nucleophosmin, an essential co-activator of Miz1 required for Miz1-induced cell-cycle arrest, in the nucleolus. Mutant forms of nucleophosmin found in acute myeloid leukaemia fail to co-activate Miz1 and re-localize it to the cytosol. As L23 is encoded by a direct target gene of Myc, this regulatory circuit may provide a feedback mechanism that links translation of Myc target genes and cell growth to Miz1-dependent cell-cycle arrest.
authors.affiliation: Institute for Molecular Biology and Tumor Research (IMT), Emil-Mannkopff-Str.2, 35033 Marburg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Wanzel
authors.forename: Annika C
authors.initials: AC
authors.lastname: Russ
authors.forename: Daniela
authors.initials: D
authors.lastname: Kleine-Kohlbrecher
authors.forename: Emanuela
authors.initials: E
authors.lastname: Colombo
authors.forename: Pier-Guiseppe
authors.initials: PG
authors.lastname: Pelicci
authors.forename: Martin
authors.initials: M
authors.lastname: Eilers
mesh_terms: D000483:Alleles; D000818:Animals; D049109:Cell Proliferation; D025461:Feedback, Physiological; D006367:HeLa Cells; D006801:Humans; D008954:Models, Biological; D050505:Mutant Proteins / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism*; D000090243:Nucleophosmin; D050828:Protein Inhibitors of Activated STAT / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D051381:Rats; D012269:Ribosomal Proteins / Q000378:metabolism*
chemical_list: D050505:Mutant Proteins; C000716967:NPM1 protein, human; D009687:Nuclear Proteins; C501001:PIAS2 protein, human; D050828:Protein Inhibitors of Activated STAT; D016271:Proto-Oncogene Proteins c-myc; D012269:Ribosomal Proteins; C032493:ribosomal protein L17; D000090243:Nucleophosmin