Akt and 14-3-3eta regulate Miz1 to control cell-cycle arrest after DNA damage.

Michael Wanzel, Daniela Kleine-Kohlbrecher, Steffi Herold, Andreas Hock, Katrien Berns, Jongsun Park, Brian Hemmings, Martin Eilers

Research output: Contribution to journalJournal articleResearchpeer-review

76 Citations (Scopus)

Abstract

The transcription factor Miz1 is required for DNA-damage-induced cell-cycle arrest. We have now identified 14-3-3eta as a gene that inhibits Miz1 function through interaction with its DNA binding domain. Binding of 14-3-3eta to Miz1 depends on phosphorylation by Akt and regulates the recovery of cells from arrest after DNA damage. Miz1 has two functions in response to DNA damage: first, it is required for upregulation of a large group of genes, a function that is regulated by c-Myc, but not by 14-3-3eta; second, Miz1 represses the expression of many genes in response to DNA damage in an Akt- and 14-3-3eta-regulated manner.
Original languageEnglish
JournalNature Cell Biology
Volume7
Issue number1
Pages (from-to)30-41
Number of pages11
ISSN1465-7392
DOIs
Publication statusPublished - 2004
Externally publishedYes

Bibliographical note

Keywords: 14-3-3 Proteins; Animals; Cell Cycle; Cell Cycle Proteins; DNA Damage; DNA-Binding Proteins; Gene Expression Regulation; Gene Library; Hela Cells; Humans; Kruppel-Like Transcription Factors; Mice; Molecular Sequence Data; NIH 3T3 Cells; Phosphorylation; Protein Binding; Protein Structure, Tertiary; Protein-Serine-Threonine Kinases; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-akt; Proto-Oncogene Proteins c-myc; Rats; Transcription Factors; Up-Regulation

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