PMID- 10102273
OWN - NLM
STAT- MEDLINE
DCOM- 19990427
LR  - 20190705
IS  - 0092-8674 (Print)
IS  - 0092-8674 (Linking)
VI  - 96
IP  - 6
DP  - 1999 Mar 19
TI  - Akt promotes cell survival by phosphorylating and inhibiting a Forkhead
      transcription factor.
PG  - 857-68
AB  - Survival factors can suppress apoptosis in a transcription-independent manner by 
      activating the serine/ threonine kinase Akt, which then phosphorylates and
      inactivates components of the apoptotic machinery, including BAD and Caspase 9.
      In this study, we demonstrate that Akt also regulates the activity of FKHRL1, a
      member of the Forkhead family of transcription factors. In the presence of
      survival factors, Akt phosphorylates FKHRL1, leading to FKHRL1's association with
      14-3-3 proteins and FKHRL1's retention in the cytoplasm. Survival factor
      withdrawal leads to FKHRL1 dephosphorylation, nuclear translocation, and target
      gene activation. Within the nucleus, FKHRL1 triggers apoptosis most likely by
      inducing the expression of genes that are critical for cell death, such as the
      Fas ligand gene.
FAU - Brunet, A
AU  - Brunet A
AD  - Children's Hospital and Department of Neurobiology, Harvard Medical School,
      Boston, Massachusetts 02115, USA.
FAU - Bonni, A
AU  - Bonni A
FAU - Zigmond, M J
AU  - Zigmond MJ
FAU - Lin, M Z
AU  - Lin MZ
FAU - Juo, P
AU  - Juo P
FAU - Hu, L S
AU  - Hu LS
FAU - Anderson, M J
AU  - Anderson MJ
FAU - Arden, K C
AU  - Arden KC
FAU - Blenis, J
AU  - Blenis J
FAU - Greenberg, M E
AU  - Greenberg ME
LA  - eng
GR  - CA43855/CA/NCI NIH HHS/United States
GR  - CA46595/CA/NCI NIH HHS/United States
GR  - HD 18655/HD/NICHD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Cell
JT  - Cell
JID - 0413066
RN  - 0 (14-3-3 Proteins)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (FASLG protein, human)
RN  - 0 (FOXO1 protein, human)
RN  - 0 (FOXO3 protein, human)
RN  - 0 (Fas Ligand Protein)
RN  - 0 (Forkhead Box Protein O1)
RN  - 0 (Forkhead Box Protein O3)
RN  - 0 (Forkhead Transcription Factors)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Proteins)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Transcription Factors)
RN  - EC 1.14.16.2 (Tyrosine 3-Monooxygenase)
RN  - EC 2.7.11.1 (AKT1 protein, human)
RN  - EC 2.7.11.1 (Protein-Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
SB  - IM
MH  - 14-3-3 Proteins
MH  - Apoptosis
MH  - Binding Sites
MH  - Cell Line, Transformed
MH  - Cell Survival
MH  - Cytoplasm/metabolism
MH  - DNA-Binding Proteins/genetics/*metabolism
MH  - Fas Ligand Protein
MH  - Forkhead Box Protein O1
MH  - Forkhead Box Protein O3
MH  - Forkhead Transcription Factors
MH  - Humans
MH  - Membrane Glycoproteins/metabolism
MH  - Phosphorylation
MH  - Protein-Serine-Threonine Kinases/*metabolism
MH  - Proteins/metabolism
MH  - Proto-Oncogene Proteins/*metabolism
MH  - Proto-Oncogene Proteins c-akt
MH  - Recombinant Fusion Proteins/genetics/metabolism
MH  - Transcription Factors/genetics/*metabolism
MH  - *Tyrosine 3-Monooxygenase
EDAT- 1999/04/02 00:00
MHDA- 1999/04/02 00:01
CRDT- 1999/04/02 00:00
PHST- 1999/04/02 00:00 [pubmed]
PHST- 1999/04/02 00:01 [medline]
PHST- 1999/04/02 00:00 [entrez]
AID - S0092-8674(00)80595-4 [pii]
AID - 10.1016/s0092-8674(00)80595-4 [doi]
PST - ppublish
SO  - Cell. 1999 Mar 19;96(6):857-68. doi: 10.1016/s0092-8674(00)80595-4.