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Nature Cell Biology 10, 1051–1061 (1 September 2008) | doi:10.1038/ncb1764

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

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.