Benitah Salvador Aznar, Frye Michaela, Glogauer Michael, Watt Fiona M
Keratinocyte Laboratory, Cancer Research UK London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3PX, UK.
Science. 2005 Aug 5;309(5736):933-5. doi: 10.1126/science.1113579.
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.
哺乳动物的表皮通过干细胞的自我更新得以维持，但其潜在机制尚不清楚。在成年小鼠表皮中删除Rho鸟苷三磷酸酶Rac1，会刺激干细胞分裂并进行终末分化，导致无法维持毛囊间表皮、毛囊和皮脂腺。Rac1通过p21激活激酶2（PAK2）磷酸化负向调节c-Myc，从而在表皮中发挥作用。我们得出结论，细胞黏附和细胞骨架的多效性调节因子在控制干细胞微环境退出方面起着关键作用，并提出Rac和Myc代表一个全局干细胞调节轴。
