The "O" class: Crafting clinical care with FoxO transcription factors

Abstract

Forkhead Transcription Factors: VitalElements in Biology and Medicine providesa unique platform for the presentation of novelwork and newinsightsinto the vital role that forkhead transcription factors play in both cellular physiology as well as clinical medicine. Internationallyrecognizedinvestigators provide their insightsand perspectives for a number of forkheadgenesand proteins that mayhavethe greatestimpact for the developmentof newstrategiesfor a broad arrayof disordersthat can involve aging, cancer, cardiacfunction, neurovascular integrity,fertility, stem celldifferentiation, cellularmetabolism, and immune system regulation. Yet, the work clearly sets a precedent for the necessity to understand the cellularand molecular function of forkheadproteins sincethis familyof transcription factors can limit aswellas foster disease progression dependingupon the cellularenvironment. With this in mind, our concludingchapterforForkhead Transcription Factors: VitalElements in BiologyandMedicine offers to highlightboth the diversityand complexityofthe forkhead transcription family byfocusing upon the manunalian forkhead transcriptionfactors of the 0 class (FoxOs) that includeFoxO1,Fox03,Fox04, andFox06. FoxOproteinsareincreasingly considered to representuniquecellular targetsthat cancontrolnumerousprocesses suchasangiogenesis, cardiovascular development, vascular tone,oxidative stress, stemcellproliferation,fertility, andimmunesurveillance. Furthermore, FoxOtranscription factors areexciting considerations for disorders suchascancerin lightoftheirpro- apoptoticandinhibitorycellcycle effects aswellasdiabetes mellitus given theclose association FoxOsholdwith cellular metabolism. In addition, thesetranscriptionfactorsareclosely integratedwithseveral novelsignal transductionpathways, suchaserythropoietin andWntproteins, that mayinfluence the abilityofFoxOsto leadto cellsurvival or cellinjury. Furtherunderstandingof both the function and intricatenatureof the forkhead transcriptionfactorfamily, and in particular the FoxOproteins,shouldallowselective regulationof cellular development or cellular demise for the generationof successful future clinical strategies and patient well-being. © 2009 Landes Bioscience and Springer Science+Business Media.