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

First Author  Herkert B Year  2010
Journal  J Cell Biol Volume  188
Issue  6 Pages  905-18
PubMed ID  20308430 Mgi Jnum  J:158803
Mgi Id  MGI:4440668 Doi  10.1083/jcb.200908103
Citation  Herkert B, et al. (2010) The Arf tumor suppressor protein inhibits Miz1 to suppress cell adhesion and induce apoptosis. J Cell Biol 188(6):905-18
abstractText  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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