title: Kat3 coactivators in somatic stem cells and cancer stem cells: biological roles, evolution, and pharmacologic manipulation.
abstract: Long-lived somatic stem cells regenerate adult tissues throughout our lifetime. However, with aging, there is a significant deterioration in the function of stem and progenitor cells, which contribute to diseases of aging. The decision for a long-lived somatic stem cell to become activated and subsequently to undergo either a symmetric or an asymmetric division is a critical cellular decision process. The decision to preferentially divide symmetrically or asymmetrically may be the major fundamental intrinsic difference between normal somatic stem cells and cancer stem cells. Based upon work done primarily in our laboratory over the past 15 years, this article provides a perspective on the critical role of somatic stem cells in aging. In particular, we discuss the importance of symmetric versus asymmetric divisions in somatic stem cells and the role of the differential usage of the highly similar Kat3 coactivators, CREB-binding protein (CBP) and p300, in stem cells. We describe and propose a more complete model for the biological mechanism and roles of these two coactivators, their evolution, and unique roles and importance in stem cell biology. Finally, we discuss the potential to pharmacologically manipulate Kat3 coactivator interactions in endogenous stem cells (both normal and cancer stem cells) to potentially ameliorate the aging process and common diseases of aging.
authors.affiliation: Division of Bioinformatics, Department of Preventive Medicine, USC Norris Comprehensive Cancer Center, 1450 Biggy Street, NRT 2501, Los Angeles, CA, 90033, USA.
authors.forename: Paul D
authors.initials: PD
authors.lastname: Thomas
authors.affiliation: USC Center for Molecular Pathways and Drug Discovery, USC Norris Comprehensive Cancer Center, 1450 Biggy Street, NRT 4501, Los Angeles, CA, 90033, USA. kahnm@usc.edu.
authors.forename: Michael
authors.initials: M
authors.lastname: Kahn
mesh_terms: D053687:Adult Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D050882:CREB-Binding Protein / Q000378:metabolism; D051177:Catenins / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D050881:E1A-Associated p300 Protein / Q000378:metabolism; D006801:Humans; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D010446:Peptide Fragments / Q000378:metabolism; D012795:Sialoglycoproteins / Q000378:metabolism; D060449:Wnt Signaling Pathway / Q000502:physiology
chemical_list: D051177:Catenins; D010446:Peptide Fragments; D012795:Sialoglycoproteins; C571744:bone sialoprotein (35-62), human; D050882:CREB-Binding Protein; C494363:CREBBP protein, human; D050881:E1A-Associated p300 Protein; C494360:EP300 protein, human
keywords: CBP; Cancer stem cells; Kat3 coactivator; Pharmacology; Somatic stem cells; p300