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...

Full description

Saved in:

Bibliographic Details
Published in:	The Journal of cell biology 2010-03, Vol.188 (6), p.905-918
Main Authors:	Herkert, Barbara, Dwertmann, Anne, Herold, Steffi, Abed, Mona, Naud, Jean-Francois, Finkernagel, Florian, Harms, Gregory S, Orian, Amir, Wanzel, Michael, Eilers, Martin
Format:	Article
Language:	eng
Subjects:	Antibodies Apoptosis Cell Adhesion Cell adhesion & migration Cell cycle Cells, Cultured Cellular immunity Gene expression Genes HeLa cells Humans Kruppel-Like Transcription Factors - metabolism Mutation Plasmids Proteins Repression Signal transduction Tumor Suppressor Protein p14ARF - metabolism Tumors Zinc
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	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.
ISSN:	0021-9525 1540-8140