Stem cell depletion through epidermal deletion of Rac1.
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.
Benitah
Salvador Aznar
SA
Keratinocyte Laboratory, Cancer Research UK London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3PX, UK.
Frye
Michaela
M
Glogauer
Michael
M
Watt
Fiona M
FM
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
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