Regulation of erythrocyte lifespan: do reactive oxygen species set the clock?
The forkhead box O (Foxo) subfamily of transcription factors regulates expression of genes important for many cellular processes, ranging from initiation of cell cycle arrest and apoptosis to induction of DNA damage repair. Invertebrate Foxo orthologs such as DAF-16 also regulate longevity. Cellular responses inducing resistance to ROS are important for cellular survival and organism lifespan, but until recently, mammalian factors regulating resistance to oxidative stress have not been well characterized. Marinkovic and colleagues demonstrate in this issue of the JCI that Foxo3 is specifically required for induction of proteins that regulate the in vivo oxidative stress response in murine erythrocytes (see the related article beginning on page 2133). Their work offers the interesting hypothesis that in so doing, Foxo3 may regulate the lifespan of red blood cells, and underlies the importance of understanding the direct targets of this transcription factor and its regulation.
Whitehead Institute for Biomedical Research, Cambridge, Massachusetts, USA.
Shilpa M
SM
Hattangadi
Harvey F
HF
Lodish
D021581:Active Transport, Cell Nucleus / Q000235:genetics; D000818:Animals; D017173:Caenorhabditis elegans / Q000166:cytology / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000096:biosynthesis; D004912:Erythrocytes / Q000166:cytology / Q000378:metabolism*; D004920:Erythropoiesis / Q000235:genetics; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000172:deficiency / Q000378:metabolism*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D051379:Mice; D008817:Mice, Mutant Strains; D008938:Mitosis / Q000235:genetics; D018384:Oxidative Stress / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014157:Transcription Factors / Q000172:deficiency / Q000378:metabolism; D014158:Transcription, Genetic / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics
D029742:Caenorhabditis elegans Proteins; C493957:Cdkn1a protein, mouse; D050759:Cyclin-Dependent Kinase Inhibitor p21; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; C474033:FoxO3 protein, mouse; D017382:Reactive Oxygen Species; D014157:Transcription Factors; C108831:daf-16 protein, C elegans