A dominant-negative mutant of c-Jun inhibits cell cycle progression during the transition of CD4-CD8- to CD4+CD8+ thymocytes Journal Article
| Authors: | King, L. B.; Tolosa, E.; Lenczowski, J. M.; Lu, F.; Lind, E. F.; Hunziker, R.; Petrie, H. T.; Ashwell, J. D. |
| Article 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 (~ 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 + G2/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: | controlled study; gene mutation; nonhuman; cd8-positive t-lymphocytes; animal cell; mouse; animals; mice; mice, knockout; cell cycle; transcription factor; cell differentiation; mice, inbred c57bl; transgenic mouse; mice, transgenic; transcription factors; gene expression regulation, developmental; lymphocyte activation; thymus; thymus gland; cell transformation; cd4-positive t-lymphocytes; t-lymphocyte subsets; thymocyte; lymphocyte count; interleukin-2; receptors, interleukin-2; protein c fos; transcription factor ap-1; mice, inbred dba; cellular differentiation; proto-oncogene proteins c-jun; priority journal; article; oncogene c jun; transgenic/knockout; genes, jun |
| Journal Title: | International Immunology |
| Volume: | 11 |
| Issue: | 8 |
| ISSN: | 0953-8178 |
| Publisher: | Oxford University Press |
| Date Published: | 1999-08-01 |
| Start Page: | 1203 |
| End Page: | 1215 |
| Language: | English |
| DOI: | 10.1093/intimm/11.8.1203 |
| PUBMED: | 10421778 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 16 August 2016 -- Source: Scopus |
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