Genetic dissection of the mechanisms underlying telomere-associated diseases: impact of the TRF2 telomeric protein on mouse epidermal stem cells.

ABSTRACT: TRF2 is a telomere-binding protein involved in the protection of chromosome ends. Interestingly, TRF2 is overexpressed in a number of human cancers. Mice with increased TRF2 expression (K5TRF2 mice) display a severe skin phenotype including an increase in skin cancer and premature skin degeneration, which includes increased skin hyperpigmentation and skin dryness; these pathologies are concomitant with dramatic telomere shortening and increased chromosomal instability. Here, we show that K5TRF2 mice have a severe epidermal stem cell (ESC) dysfunction, which is reversed by abrogation of p53 in the absence of rescue of telomere length. Importantly, p53 deletion also rescues severe skin hyperpigmentation in these mice through regulation of alpha-melanocyte-stimulating hormone (alpha-MSH). In

SUBMITTER: Stout GJ 

PROVIDER: S-EPMC2650195 | biostudies-literature | 2009 Mar-Apr

REPOSITORIES: biostudies-literature