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A dominant-negative mutant of c-Jun inhibits cell cycle progression during the transition of CD4(-)CD8(-) to CD4(+)CD8(+) thymocytes.




 

Int Immunol. 1999 Aug;11(8):1203-16. Unique Identifier : AIDSLINE

While Jun/Fos-containing transcription factors are known to be necessary for many TCR-mediated events in mature T cells, relatively little is known about their roles in thymocyte development. We have generated transgenic mice that express a trans-dominant-negative mutant of c-Jun (TAM-67) specifically in thymocytes. Expression of TAM-67 inhibited the up-regulation of AP-1-responsive genes such as c-jun and IL-2 in stimulated thymocytes from transgenic mice. In addition, altered thymocyte development in TAM-67-expressing mice was revealed by a decrease in thymic cellularity ( approximately 50%) which could be accounted for primarily by a reduction in the number of CD4(+)CD8(+) thymocytes, a large percentage of which retained CD25. The decrease in the number of CD4(+)CD8(+) thymocytes did not appear to be due to an enhanced rate of apoptosis but rather to a decrease in the number of CD4(-)CD8(-)CD25(-) cells in the S + G(2)/M stages of the cell cycle. These results indicate that Jun/Fos-containing transcription factors promote the proliferative burst that accompanies the transition from the CD4(-)CD8(-) to the CD4(+)CD8(+) stage of thymocyte development.

JOURNAL ARTICLE Animal Cell Cycle Cell Differentiation CD4-Positive T-Lymphocytes/*CYTOLOGY CD8-Positive T-Lymphocytes/*CYTOLOGY Gene Expression Regulation, Developmental *Genes, jun Interleukin-2/GENETICS/METABOLISM Lymphocyte Transformation Mice Mice, Inbred C57BL Mice, Inbred DBA Mice, Knockout Mice, Transgenic Proto-Oncogene Proteins c-jun/GENETICS/*PHYSIOLOGY Receptors, Interleukin-2/METABOLISM Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. T-Lymphocyte Subsets/*CYTOLOGY Thymus Gland/*CYTOLOGY/EMBRYOLOGY Transcription Factor AP-1/GENETICS/*METABOLISM Transcription Factors/METABOLISM



 




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