title: TAp63 prevents premature aging by promoting adult stem cell maintenance.
abstract: The cellular mechanisms that regulate the maintenance of adult tissue stem cells are still largely unknown. We show here that the p53 family member, TAp63, is essential for maintenance of epidermal and dermal precursors and that, in its absence, these precursors senesce and skin ages prematurely. Specifically, we have developed a TAp63 conditional knockout mouse and used it to ablate TAp63 in the germline (TAp63(-/-)) or in K14-expressing cells in the basal layer of the epidermis (TAp63(fl/fl);K14cre+). TAp63(-/-) mice age prematurely and develop blisters, skin ulcerations, senescence of hair follicle-associated dermal and epidermal cells, and decreased hair morphogenesis. These phenotypes are likely due to loss of TAp63 in dermal and epidermal precursors since both cell types show defective proliferation, early senescence, and genomic instability. These data indicate that TAp63 serves to maintain adult skin stem cells by regulating cellular senescence and genomic stability, thereby preventing premature tissue aging.
authors: Department of Molecular and Cellular Oncology, Graduate School of Biomedical Sciences, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors: Xiaohua
authors: X
authors: Su
authors: Maryline
authors: M
authors: Paris
authors: Young Jin
authors: YJ
authors: Gi
authors: Kenneth Y
authors: KY
authors: Tsai
authors: Min Soon
authors: MS
authors: Cho
authors: Yu-Li
authors: YL
authors: Lin
authors: Jeffrey A
authors: JA
authors: Biernaskie
authors: Satrajit
authors: S
authors: Sinha
authors: Carol
authors: C
authors: Prives
authors: Larysa H
authors: LH
authors: Pevny
authors: Freda D
authors: FD
authors: Miller
authors: Elsa R
authors: ER
authors: Flores
mesh_terms: D053687:Adult Stem Cells / Q000166:cytology / Q000502:physiology*; D019588:Aging, Premature / Q000209:etiology* / Q000473:pathology; D000818:Animals; D016922:Cellular Senescence; D004249:DNA Damage; D020405:Dermis / Q000166:cytology*; D000078404:Epidermal Cells; D016158:Genes, p53; D042822:Genomic Instability; D018859:Hair Follicle / Q000166:cytology; D015603:Keratinocytes / Q000166:cytology; D051379:Mice; D018345:Mice, Knockout; D010750:Phosphoproteins / Q000235:genetics* / Q000502:physiology*; D015595:Skin Aging / Q000235:genetics / Q000473:pathology; D015534:Trans-Activators / Q000235:genetics* / Q000502:physiology*; D014945:Wound Healing / Q000235:genetics
chemical_list: D010750:Phosphoproteins; D015534:Trans-Activators; C486419:Trp63 protein, mouse