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The Arf tumor suppressor protein inhibits Miz1 to suppress cell adhesion and induce apoptosis

Oncogenic stress induces expression of the alternate reading frame (Arf) tumor suppressor protein. Arf then stabilizes p53, which leads to cell cycle arrest or apoptosis. The mechanisms that distinguish both outcomes are incompletely understood. In this study, we show that Arf interacts with the Myc...

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Autores principales: Herkert, Barbara, Dwertmann, Anne, Herold, Steffi, Abed, Mona, Naud, Jean-Francois, Finkernagel, Florian, Harms, Gregory S., Orian, Amir, Wanzel, Michael, Eilers, Martin
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2845071/
https://www.ncbi.nlm.nih.gov/pubmed/20308430
http://dx.doi.org/10.1083/jcb.200908103
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author Herkert, Barbara
Dwertmann, Anne
Herold, Steffi
Abed, Mona
Naud, Jean-Francois
Finkernagel, Florian
Harms, Gregory S.
Orian, Amir
Wanzel, Michael
Eilers, Martin
author_facet Herkert, Barbara
Dwertmann, Anne
Herold, Steffi
Abed, Mona
Naud, Jean-Francois
Finkernagel, Florian
Harms, Gregory S.
Orian, Amir
Wanzel, Michael
Eilers, Martin
author_sort Herkert, Barbara
collection PubMed
description Oncogenic stress induces expression of the alternate reading frame (Arf) tumor suppressor protein. Arf then stabilizes p53, which leads to cell cycle arrest or apoptosis. The mechanisms that distinguish both outcomes are incompletely understood. In this study, we show that Arf interacts with the Myc-associated zinc finger protein Miz1. Binding of Arf disrupts the interaction of Miz1 with its coactivator, nucleophosmin, induces the sumoylation of Miz1, and facilitates the assembly of a heterochromatic complex that contains Myc and trimethylated H3K9 in addition to Miz1. Arf-dependent assembly of this complex leads to the repression of multiple genes involved in cell adhesion and signal transduction and induces apoptosis. Our data point to a tumor-suppressive pathway that weakens cell–cell and cell–matrix interactions in response to expression of Arf and that may thereby facilitate the elimination of cells harboring an oncogenic mutation.
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spelling pubmed-28450712010-09-22 The Arf tumor suppressor protein inhibits Miz1 to suppress cell adhesion and induce apoptosis Herkert, Barbara Dwertmann, Anne Herold, Steffi Abed, Mona Naud, Jean-Francois Finkernagel, Florian Harms, Gregory S. Orian, Amir Wanzel, Michael Eilers, Martin J Cell Biol Research Articles Oncogenic stress induces expression of the alternate reading frame (Arf) tumor suppressor protein. Arf then stabilizes p53, which leads to cell cycle arrest or apoptosis. The mechanisms that distinguish both outcomes are incompletely understood. In this study, we show that Arf interacts with the Myc-associated zinc finger protein Miz1. Binding of Arf disrupts the interaction of Miz1 with its coactivator, nucleophosmin, induces the sumoylation of Miz1, and facilitates the assembly of a heterochromatic complex that contains Myc and trimethylated H3K9 in addition to Miz1. Arf-dependent assembly of this complex leads to the repression of multiple genes involved in cell adhesion and signal transduction and induces apoptosis. Our data point to a tumor-suppressive pathway that weakens cell–cell and cell–matrix interactions in response to expression of Arf and that may thereby facilitate the elimination of cells harboring an oncogenic mutation. The Rockefeller University Press 2010-03-22 /pmc/articles/PMC2845071/ /pubmed/20308430 http://dx.doi.org/10.1083/jcb.200908103 Text en © 2010 Herkert et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Research Articles
Herkert, Barbara
Dwertmann, Anne
Herold, Steffi
Abed, Mona
Naud, Jean-Francois
Finkernagel, Florian
Harms, Gregory S.
Orian, Amir
Wanzel, Michael
Eilers, Martin
The Arf tumor suppressor protein inhibits Miz1 to suppress cell adhesion and induce apoptosis
title The Arf tumor suppressor protein inhibits Miz1 to suppress cell adhesion and induce apoptosis
title_full The Arf tumor suppressor protein inhibits Miz1 to suppress cell adhesion and induce apoptosis
title_fullStr The Arf tumor suppressor protein inhibits Miz1 to suppress cell adhesion and induce apoptosis
title_full_unstemmed The Arf tumor suppressor protein inhibits Miz1 to suppress cell adhesion and induce apoptosis
title_short The Arf tumor suppressor protein inhibits Miz1 to suppress cell adhesion and induce apoptosis
title_sort arf tumor suppressor protein inhibits miz1 to suppress cell adhesion and induce apoptosis
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2845071/
https://www.ncbi.nlm.nih.gov/pubmed/20308430
http://dx.doi.org/10.1083/jcb.200908103
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