A ribosomal protein L23-nucleophosmin circuit coordinates Mizl function with cell growth.
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.
Wanzel
Michael
M
Institute for Molecular Biology and Tumor Research (IMT), Emil-Mannkopff-Str.2, 35033 Marburg, Germany.
Russ
Annika C
AC
Kleine-Kohlbrecher
Daniela
D
Colombo
Emanuela
E
Pelicci
Pier-Guiseppe
PG
Eilers
Martin
M
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*
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