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 language | English |
|---|---|
| Pages (from-to) | 1051-1061 |
| Number of pages | 11 |
| Journal | Nature Cell Biology |
| Volume | 10 |
| Issue number | 9 |
| DOIs | |
| Publication status | Published - 2008 |
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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 journal › Article
}
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 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=51049097902&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=51049097902&partnerID=8YFLogxK
U2 - 10.1038/ncb1764
DO - 10.1038/ncb1764
M3 - Article
C2 - 19160485
AN - SCOPUS:51049097902
VL - 10
SP - 1051
EP - 1061
JO - Nature Cell Biology
JF - Nature Cell Biology
SN - 1465-7392
IS - 9
ER -