Wanzel Michael, Kleine-Kohlbrecher Daniela, Herold Steffi, Hock Andreas, Berns Katrien, Park Jongsun, Hemmings Brian, Eilers Martin
Institute for Molecular Biology and Tumor Research, University of Marburg, Emil-Mannkopff-Strasse 2, 35033 Marburg, Germany.
Nat Cell Biol. 2005 Jan;7(1):30-41. doi: 10.1038/ncb1202. Epub 2004 Dec 5.
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.
转录因子Miz1是DNA损伤诱导的细胞周期停滞所必需的。我们现已确定14-3-3η是一个通过与其DNA结合域相互作用来抑制Miz1功能的基因。14-3-3η与Miz1的结合依赖于Akt的磷酸化，并调节DNA损伤后细胞从停滞状态的恢复。Miz1在应对DNA损伤时有两个功能：第一，它是上调一大组基因所必需的，这一功能由c-Myc调节，而非14-3-3η；第二，Miz1以Akt和14-3-3η调节的方式抑制许多基因对DNA损伤的反应表达。
