3D Tissue Models

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

TypeWhite Paper Summary

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.

Name:Devin Leake
Name:Alan R Horwitz
Name:Jessica Zareno
Name:Martin Eilers
Name:Joan S Brugge
Name:Anastasia Khvorova
Name:Angela Reynolds
Name:Alex Mogilner
Organization:Virginia Commonwealth University

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