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

Standard

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 journalSCORING: Journal articleResearchpeer-review

Harvard

King, LB, Tolosa, E, Lenczowski, JM, Lu, F, Lind, EF, Hunziker, R, Petrie, HT & Ashwell, JD 1999, 'A dominant-negative mutant of c-Jun inhibits cell cycle progression during the transition of CD4(-)CD8(-) to CD4(+)CD8(+) thymocytes', INT IMMUNOL, vol. 11, no. 8, pp. 1203-16.

APA

King, L. B., Tolosa, E., Lenczowski, J. M., Lu, F., Lind, E. F., Hunziker, R., Petrie, H. T., & Ashwell, J. D. (1999). A dominant-negative mutant of c-Jun inhibits cell cycle progression during the transition of CD4(-)CD8(-) to CD4(+)CD8(+) thymocytes. INT IMMUNOL, 11(8), 1203-16.

Vancouver

Bibtex

@article{d8ab9874977740cba65803f892cd6371,
title = "A dominant-negative mutant of c-Jun inhibits cell cycle progression during the transition of CD4(-)CD8(-) to CD4(+)CD8(+) thymocytes",
abstract = "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.",
keywords = "Animals, CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Cell Cycle, Cell Differentiation, Gene Expression Regulation, Developmental, Genes, jun, Interleukin-2, Lymphocyte Activation, Mice, Mice, Inbred C57BL, Mice, Inbred DBA, Mice, Knockout, Mice, Transgenic, Proto-Oncogene Proteins c-jun, Receptors, Interleukin-2, T-Lymphocyte Subsets, Thymus Gland, Transcription Factor AP-1, Transcription Factors",
author = "King, {L B} and E Tolosa and Lenczowski, {J M} and F Lu and Lind, {E F} and R Hunziker and Petrie, {H T} and Ashwell, {J D}",
year = "1999",
month = aug,
day = "1",
language = "English",
volume = "11",
pages = "1203--16",
journal = "INT IMMUNOL",
issn = "0953-8178",
publisher = "Oxford University Press",
number = "8",

}

RIS

TY - JOUR

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 -