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P53 regulates T cell development through Notch1


, : P53 regulates T cell development through Notch1. FASEB Journal 16(4): A343, March 20

p53-/- mice have been shown to have a high rate of lymphoma formation in the T cell lineage. It has been reported that Presenilin (PS) expression is elevated in p53-/- mice, and cleavage by PS activates Notch1, a protein thought to promote the development of CD8+ T cells. To ascertain if Notch1 activation is altered in the absence of p53, Notch1 expression and cleavage were analyzed in p53-/- thymoma lines. The level of Notch1 activation and expression is significantly higher in p53-/- thymoma lines as compared to wild-type thymocytes. PS1 expression is increased in these thymoma lines, which is consistent with data from other systems regarding PS levels in the absence of p53. To determine if p53 is involved in regulating T cell development via Notch activation, CD4/CD8 ratios were examined in thymocytes and splenocytes from p53-null mice. A dramatic decrease in the CD4/CD8 ratio was observed in both p53-/- thymocytes and splenocytes. These results indicate that p53-mediated suppression of PS1 effects the lineage commitment of CD4+CD8+ T cells by reducing the number of CD8+ cells that develop, and that reduction is observed in the thymus as well as the periphery.

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