Article abstract
Nature Cell Biology 10, 1051 - 1061 (2008)
Published online: 1 August 2008 | doi:10.1038/ncb1764
A ribosomal protein L23-nucleophosmin circuit coordinates Miz1 function with cell growth
Michael Wanzel1, Annika C. Russ1, Daniela Kleine-Kohlbrecher2, Emanuela Colombo3, Pier-Guiseppe Pelicci3 & Martin Eilers1
Abstract
The Myc-associated zinc-finger protein, Miz1, is a negative regulator of cell proliferation and induces expression of the cell-cycle inhibitors p15Ink4b and p21Cip1. 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.
- Institute for Molecular Biology and Tumor Research (IMT), Emil-Mannkopff-Str.2, 35033 Marburg; Germany.
- Biotech Research and Innovation Centre (BRIC), Copenhagen Biocenter; Ole Maaløes Vej 5, DK-2200 Copenhagen N, Denmark.
- Department of Experimental Oncology, Instituto Europeo di Oncologia, Via Ripamonti 435; 20141 Milan, Italy.
Correspondence to: Martin Eilers1 e-mail: eilers@imt.uni-marburg.de
MORE ARTICLES LIKE THIS
These links to content published by NPG are automatically generated.
RESEARCH
The leukemia-associated cytoplasmic nucleophosmin mutant is an oncogene with paradoxical functions: Arf inactivation and induction of cellular senescenceOncogene Original Article
Binding to nucleophosmin determines the localization of human and chicken ARF but not its impact on p53Oncogene Original Article
Influence of nucleophosmin/B23 on DNA binding and transcriptional activity of the androgen receptor in prostate cancer cellOncogene Original Article
Identification and functional characterization of a cytoplasmic nucleophosmin leukaemic mutant generated by a novel exon-11 NPM1 mutationLeukemia Letter
See all 6 matches for Research
