title: Stem cell depletion through epidermal deletion of Rac1.
abstract: Mammalian epidermis is maintained by self-renewal of stem cells, but the underlying mechanisms are unknown. Deletion of Rac1, a Rho guanosine triphosphatase, in adult mouse epidermis stimulated stem cells to divide and undergo terminal differentiation, leading to failure to maintain the interfollicular epidermis, hair follicles, and sebaceous glands. Rac1 exerts its effects in the epidermis by negatively regulating c-Myc through p21-activated kinase 2 (PAK2) phosphorylation. We conclude that a pleiotropic regulator of cell adhesion and the cytoskeleton plays a critical role in controlling exit from the stem cell niche and propose that Rac and Myc represent a global stem cell regulatory axis.
authors.affiliation: Keratinocyte Laboratory, Cancer Research UK London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3PX, UK.
authors.forename: Salvador Aznar
authors.initials: SA
authors.lastname: Benitah
authors.forename: Michaela
authors.initials: M
authors.lastname: Frye
authors.forename: Michael
authors.initials: M
authors.lastname: Glogauer
authors.forename: Fiona M
authors.initials: FM
authors.lastname: Watt
mesh_terms: D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism; D017209:Apoptosis; D002294:Carcinoma, Squamous Cell / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D000078404:Epidermal Cells; D017353:Gene Deletion; D006801:Humans; D015603:Keratinocytes; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009479:Neuropeptides / Q000235:genetics / Q000502:physiology*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D012878:Skin Neoplasms / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology*; D013629:Tamoxifen / Q000031:analogs & derivatives*; D054462:p21-Activated Kinases; D020744:rac GTP-Binding Proteins / Q000235:genetics / Q000502:physiology*; D020830:rac1 GTP-Binding Protein
chemical_list: D000943:Antigens, Differentiation; C489427:MYC protein, human; C489428:Myc protein, mouse; D009479:Neuropeptides; D016271:Proto-Oncogene Proteins c-myc; C484602:Rac1 protein, mouse; D013629:Tamoxifen; C016601:afimoxifene; C515907:PAK2 protein, human; C515909:Pak2 protein, mouse; D017346:Protein Serine-Threonine Kinases; D054462:p21-Activated Kinases; D020744:rac GTP-Binding Proteins; D020830:rac1 GTP-Binding Protein