Nucleolar Arf sequesters Mdm2 and activates p53
JD Weber, LJ Taylor, MF Roussel, CJ Sherr… - Nature cell …, 1999 - nature.com
JD Weber, LJ Taylor, MF Roussel, CJ Sherr, D Bar-Sagi
Nature cell biology, 1999•nature.comAbstract The Ink4/Arf locus encodes two tumour-suppressor proteins, p16 Ink4a and p19 Arf,
that govern the antiproliferative functions of the retinoblastoma and p53 proteins,
respectively. Here we show that Arf binds to the product of the Mdm2 gene and sequesters it
into the nucleolus, thereby preventing negative-feedback regulation of p53 by Mdm2 and
leading to the activation of p53 in the nucleoplasm. Arf and Mdm2 co-localize in the
nucleolus in response to activation of the oncoprotein Myc and as mouse fibroblasts …
that govern the antiproliferative functions of the retinoblastoma and p53 proteins,
respectively. Here we show that Arf binds to the product of the Mdm2 gene and sequesters it
into the nucleolus, thereby preventing negative-feedback regulation of p53 by Mdm2 and
leading to the activation of p53 in the nucleoplasm. Arf and Mdm2 co-localize in the
nucleolus in response to activation of the oncoprotein Myc and as mouse fibroblasts …
Abstract
The Ink4/Arf locus encodes two tumour-suppressor proteins, p16 Ink4a and p19 Arf, that govern the antiproliferative functions of the retinoblastoma and p53 proteins, respectively. Here we show that Arf binds to the product of the Mdm2 gene and sequesters it into the nucleolus, thereby preventing negative-feedback regulation of p53 by Mdm2 and leading to the activation of p53 in the nucleoplasm. Arf and Mdm2 co-localize in the nucleolus in response to activation of the oncoprotein Myc and as mouse fibroblasts undergo replicative senescence. These topological interactions of Arf and Mdm2 point towards a new mechanism for p53 activation.
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