A dominant-negative mutant of c-Jun inhibits cell cycle progression during the transition of CD4(-)CD8(-) to CD4(+)CD8(+) thymocytes
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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. / King, L B; Tolosa, E; Lenczowski, J M; Lu, F; Lind, E F; Hunziker, R; Petrie, H T; Ashwell, J D.
In: INT IMMUNOL, Vol. 11, No. 8, 01.08.1999, p. 1203-16.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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T1 - A dominant-negative mutant of c-Jun inhibits cell cycle progression during the transition of CD4(-)CD8(-) to CD4(+)CD8(+) thymocytes
AU - King, L B
AU - Tolosa, E
AU - Lenczowski, J M
AU - Lu, F
AU - Lind, E F
AU - Hunziker, R
AU - Petrie, H T
AU - Ashwell, J D
PY - 1999/8/1
Y1 - 1999/8/1
N2 - 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.
AB - 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.
KW - Animals
KW - CD4-Positive T-Lymphocytes
KW - CD8-Positive T-Lymphocytes
KW - Cell Cycle
KW - Cell Differentiation
KW - Gene Expression Regulation, Developmental
KW - Genes, jun
KW - Interleukin-2
KW - Lymphocyte Activation
KW - Mice
KW - Mice, Inbred C57BL
KW - Mice, Inbred DBA
KW - Mice, Knockout
KW - Mice, Transgenic
KW - Proto-Oncogene Proteins c-jun
KW - Receptors, Interleukin-2
KW - T-Lymphocyte Subsets
KW - Thymus Gland
KW - Transcription Factor AP-1
KW - Transcription Factors
M3 - SCORING: Journal article
C2 - 10421778
VL - 11
SP - 1203
EP - 1216
JO - INT IMMUNOL
JF - INT IMMUNOL
SN - 0953-8178
IS - 8
ER -