PMID- 10358014
OWN - NLM
STAT- MEDLINE
DCOM- 19990706
LR  - 20190508
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 24
DP  - 1999 Jun 11
TI  - Negative regulation of the forkhead transcription factor FKHR by Akt.
PG  - 16741-6
AB  - The FKHR gene was first identified from its disruption by the t(2;13) chromosomal
      translocation seen in the pediatric tumor alveolar rhabdomyosarcoma. It encodes
      for a member of the forkhead family of transcription factors. Recently, a homolog
      of FKHR in the nematode Caenorhabditis elegans was identified called DAF-16,
      which is a downstream target of two Akt homologs in an insulin-related signaling 
      pathway. We have examined the possible role of Akt in the regulation of FKHR. We 
      find that FKHR can bind in vitro to the insulin-responsive sequence (IRS) in the 
      insulin-like growth factor-binding protein 1 promoter and can activate
      transcription from a reporter plasmid containing multiple copies of the IRS.
      Expression of active but not inactive Akt can suppress FKHR-mediated
      transcriptional activation. Akt can phosphorylate FKHR in vitro on three
      phosphoacceptor sites, at least a subset of which can also be phosphorylated by
      Akt in vivo. Importantly, mutation of these three sites to alanine residues
      enhances the transcriptional activity of FKHR and renders it resistant to
      inhibition by Akt. Expression of an Akt-resistant mutant of FKHR causes apoptosis
      in 293T cells in a manner dependent on DNA binding. These results suggest that
      FKHR may be a direct nuclear regulatory target for Akt in both metabolic and cell
      survival pathways.
FAU - Tang, E D
AU  - Tang ED
AD  - Department of Biological Chemistry, University of Michigan Medical School Ann
      Arbor, Michigan 48109, USA. edtang@unich.edu
FAU - Nunez, G
AU  - Nunez G
FAU - Barr, F G
AU  - Barr FG
FAU - Guan, K L
AU  - Guan KL
LA  - eng
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Insulin-Like Growth Factor Binding Protein 1)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Transcription Factors)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.11.1 (Protein-Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
SB  - IM
MH  - Amino Acid Sequence
MH  - Apoptosis
MH  - Consensus Sequence
MH  - DNA-Binding Proteins/*metabolism
MH  - Genes, Reporter
MH  - Insulin-Like Growth Factor Binding Protein 1/*biosynthesis/genetics
MH  - Molecular Sequence Data
MH  - Phosphorylation
MH  - Protein Binding
MH  - Protein Kinases/*metabolism
MH  - *Protein-Serine-Threonine Kinases
MH  - Proto-Oncogene Proteins/*metabolism
MH  - Proto-Oncogene Proteins c-akt
MH  - Recombinant Fusion Proteins/metabolism
MH  - Response Elements
MH  - Transcription Factors/*metabolism
MH  - Transcription, Genetic
MH  - *Transcriptional Activation
EDAT- 1999/06/08 00:00
MHDA- 1999/06/08 00:01
CRDT- 1999/06/08 00:00
PHST- 1999/06/08 00:00 [pubmed]
PHST- 1999/06/08 00:01 [medline]
PHST- 1999/06/08 00:00 [entrez]
AID - 10.1074/jbc.274.24.16741 [doi]
PST - ppublish
SO  - J Biol Chem. 1999 Jun 11;274(24):16741-6. doi: 10.1074/jbc.274.24.16741.