A ribosomal protein L23-nucleophosmin circuit coordinates Miz1 function with cell growth

Michael Wanzel, Annika C. Russ, Daniela Kleine-Kohlbrecher, Emanuela Colombo, Pier Guiseppe Pelicci, Martin Eilers

Research output: Contribution to journalArticle

77 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1051-1061
Number of pages11
JournalNature Cell Biology
Volume10
Issue number9
DOIs
Publication statusPublished - 2008

Fingerprint

myc Genes
Cell Cycle Checkpoints
Ribosomal Proteins
Zinc Fingers
Regulator Genes
Growth
Acute Myeloid Leukemia
Cytosol
Transcriptional Activation
Cell Cycle
Cell Proliferation
Proteins
ribosomal protein L7-L12
nucleophosmin

ASJC Scopus subject areas

  • Cell Biology

Cite this

A ribosomal protein L23-nucleophosmin circuit coordinates Miz1 function with cell growth. / Wanzel, Michael; Russ, Annika C.; Kleine-Kohlbrecher, Daniela; Colombo, Emanuela; Pelicci, Pier Guiseppe; Eilers, Martin.

In: Nature Cell Biology, Vol. 10, No. 9, 2008, p. 1051-1061.

Research output: Contribution to journalArticle

Wanzel, Michael ; Russ, Annika C. ; Kleine-Kohlbrecher, Daniela ; Colombo, Emanuela ; Pelicci, Pier Guiseppe ; Eilers, Martin. / A ribosomal protein L23-nucleophosmin circuit coordinates Miz1 function with cell growth. In: Nature Cell Biology. 2008 ; Vol. 10, No. 9. pp. 1051-1061.
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