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

TY - JOUR

T1 - A ribosomal protein L23-nucleophosmin circuit coordinates Miz1 function with cell growth

AU - Wanzel, Michael

AU - Russ, Annika C

AU - Kleine-Kohlbrecher, Daniela

AU - Colombo, Emanuela

AU - Pelicci, Pier-Guiseppe

AU - Eilers, Martin

PY - 2008

Y1 - 2008

N2 - 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.

AB - 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.

U2 - 10.1038/ncb1764

DO - 10.1038/ncb1764

M3 - Journal article

C2 - 18677304

SN - 1465-7392

JO - Nature Cell Biology

JF - Nature Cell Biology

ER -