Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2003-5-29
pubmed:abstractText
Forkhead transcription factors of the FOXO family are important downstream targets of protein kinase B (PKB)/Akt, a kinase shown to play a decisive role in cell proliferation and cell survival. Direct phosphorylation by PKB/Akt inhibits transcriptional activation by FOXO factors, causing their displacement from the nucleus into the cytoplasm. Work from recent years has shown that this family of transcription factors regulates the expression of a number of genes that are crucial for the proliferative status of a cell, as well as a number of genes involved in programmed cell death. As such, these transcription factors appear to play an essential role in many of the effects of PKB/Akt on cell proliferation and survival. Indeed, in cells of the hematopoietic system, mere activation of a FOXO factor is sufficient to activate a variety of proapoptotic genes and to trigger apoptosis. In contrast, in most other cell types, activation of FOXO blocks cellular proliferation and drives cells into a quiescent state. In such cell types, FOXO factors also provide the protective mechanisms that are required to adapt to the altered metabolic state of quiescent cells. Thus, as PKB/Akt signaling is switched off, FOXO factors take over to determine the fate of a cell, long-term survival in a quiescent state, or programmed cell death. This review summarizes our current understanding of the mechanisms by which PKB/Akt and FOXO factors regulate these decisions.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0741-5400
pubmed:author
pubmed:issnType
Print
pubmed:volume
73
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
689-701
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
Decisions on life and death: FOXO Forkhead transcription factors are in command when PKB/Akt is off duty.
pubmed:affiliation
Department of Physiological Chemistry and Center for Biomedical Genetics, University Medical Center Utrecht, The Netherlands. r.medema@nki.nl
pubmed:publicationType
Journal Article, Review, Research Support, Non-U.S. Gov't