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Updated: Aug 20, 2026

Studying Cell Cycle-regulated Gene Expression by Two Complementary Cell Synchronization Protocols
Published on: June 6, 2017
Akt and 14-3-3eta regulate Miz1 to control cell-cycle arrest after DNA damage
Michael Wanzel1, Daniela Kleine-Kohlbrecher, Steffi Herold
1Institute for Molecular Biology and Tumor Research, University of Marburg, Emil-Mannkopff-Strasse 2, 35033 Marburg, Germany.
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.
Insights
The transcription factor Miz1 halts cell-cycle progression after DNA damage. A newly identified gene, 14-3-3eta, inhibits Miz1, impacting cell recovery from DNA damage arrest.
Area of Science:
- Molecular Biology
- Cell Biology
- Cancer Research
Background:
- The transcription factor Miz1 plays a crucial role in DNA-damage-induced cell-cycle arrest.
- Understanding the regulation of Miz1 is vital for comprehending cellular responses to DNA damage.
Purpose of the Study:
- To identify novel regulators of Miz1 function in response to DNA damage.
- To elucidate the mechanism by which Miz1's function is modulated, affecting cell-cycle arrest and recovery.
Main Methods:
- Identification of interacting partners of Miz1.
- Analysis of gene expression changes upon DNA damage.
- Investigation of protein-protein interactions and phosphorylation events (Akt).
Main Results:
- 14-3-3eta was identified as a novel inhibitor of Miz1.
- 14-3-3eta binds to Miz1's DNA binding domain, dependent on Akt phosphorylation.
- Miz1 exhibits dual roles: c-Myc-regulated gene upregulation and Akt/14-3-3eta-regulated gene repression.
Conclusions:
- 14-3-3eta negatively regulates Miz1's role in repressing gene expression during DNA damage response.
- Akt-mediated phosphorylation of Miz1 is critical for 14-3-3eta binding and modulation of gene repression.
- This interaction impacts the cell's ability to recover from DNA damage-induced arrest.
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