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Summary Gab1 is a scaffold protein that acts downstream of receptor tyrosine kinases. Here, we produced conditional Gab1 mutant mice (by K14- and Krox20-cre ) and show that Gab1 mediates crucial signals in the control of both the hair cycle and the self-renewal of hair follicle stem cells. Remarkably, mutant hair follicles do not enter catagen, the destructive phase of the hair cycle. Instead, hair follicle stem cells lose quiescence and become exhausted, and thus no stem cell niches are established in the bulges. Moreover, conditional sustained activation of Mapk signaling by expression of a gain-of-function Mek1 DD allele (by Krox20-cre ) rescues hair cycle deficits and restores quiescence of the stem cells. Our data thus demonstrate an essential role of Gab1 downstream of receptor tyrosine kinases and upstream of Shp2 and Mapk in the regulation of the hair cycle and the self-renewal of hair follicle stem cells. [ABSTRACT FROM AUTHOR]

Abstract: Human thioredoxin reductase (TrxR) system is associated with cancer cell growth and anti-apoptosis process. Effects of 1, 2-[bis (1,2-Benzisoselenazolone-3 (2H) -ketone)]ethane (BBSKE), a novel TrxR inhibitor, were investigated on A549, HeLa, Bel-7402, BGC823 and KB cell lines. After treated with BBSKE, a good linear correlation coefficient (r≥0.989) between TrxR activity and cell viability exists in each cell line together with cell growth/proliferation inhibition and apoptosis through Bcl-2/Bax and Caspase-3 pathways. These results suggest that there exists some relationship between TrxR inactivation and growth/proliferation inhibition or apoptosis in the investigated cell lines. [Copyright &y& Elsevier]