FOXO transcription factors in cell-cycle regulation and the response to oxidative stress.
Mammalian forkhead members of the class O (FOXO) transcription factors, including FOXO1, FOXO3a, and FOXO4, are implicated in the regulation of a variety of cellular processes, including the cell cycle, apoptosis, DNA repair, stress resistance, and metabolism. FOXO proteins are negatively regulated by the phosphatidylinositol 3-kinase-Akt signaling pathway, which is activated by growth factors and cytokines. Recent studies indicate that the activities of FOXO proteins are also regulated by oxidative stress, which induces their phosphorylation, translocation to the nucleus, and acetylation-deacetylation. Similar to the tumor suppressor p53, FOXO is activated by stress and induces the expression of genes that contribute to cell-cycle arrest, suggesting that it also functions as a tumor suppressor.
Furukawa-Hibi
Yoko
Y
Department of Geriatric Research, National Institute for Longevity Sciences, National Center for Geriatrics and Gerontology, Morioka, Obu, Aichi, Japan.
Kobayashi
Yosuke
Y
Chen
Chen
C
Motoyama
Noboru
N
D000818:Animals; D002453:Cell Cycle; D051858:Forkhead Transcription Factors; D006801:Humans; D009687:Nuclear Proteins / Q000145:classification / Q000378:metabolism*; D018384:Oxidative Stress; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D015398:Signal Transduction; D014157:Transcription Factors / Q000145:classification / Q000378:metabolism*
D051858:Forkhead Transcription Factors; D009687:Nuclear Proteins; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D014157:Transcription Factors; C494918:AKT1 protein, human