Institute for Molecular Biology and Tumor Research, University
of Marburg, Emil-Mannkopff-Strasse 2, 35033 Marburg,
Germany.
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.
School of Life Sciences and Biotechnology, Korea University, Seoul 136-701, Republic of Korea.
Annexin-A1 (ANX-1) is involved in glucocorticoid
receptor (GR)-mediated signal transduction. However, the molecular
mechanism by which ANX-1 plays a role in GR signaling is not fully
understood. Recently, we reported that 14-3-3eta inhibits degradation of
GR, resulting in an increase in GR transcriptional activity. In this study,
we have addressed the role of ANX-1 in 14-3-3eta-induced enhancement of GR transactivation. ANX-1 abolished the increase in GR
transcriptional activity due to 14-3-3eta. ANX-1 had no effect on the
protein level of GR. However, ANX-1 abrogated the inhibitory effect of
14-3-3eta on GR degradation, which causes a decrease in GR stability in the
nucleus. Our results indicate that ANX-1 functions as a negative regulator
of GR transcriptional activation by inhibiting 14-3-3eta-induced
up-regulation of GR.
Institute for Molecular Biology and Tumor Research, University
of Marburg, Emil-Mannkopff-Strasse 2, 35033 Marburg,
Germany.
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.
