Regulation of c-jun gene expression in human T lymphocytes.
The present studies have examined the effects of mitogens on induction of early response gene expression in normal peripheral blood T and Jurkat cells. Pokeweed mitogen (PWM) or anti-CD3 significantly increases c-jun messenger RNA (mRNA) levels in T cells. This transient PWM-related increase in c-jun transcripts is maximal after 15 to 30 minutes of exposure of T cells to PWM. PWM induces c-jun gene expression in a concentration-dependent manner. Moreover, PWM similarly induces expression of other genes coding for leucine zipper transcription factors, ie, jun-B and c-fos. Nuclear run on assays demonstrate that PWM treatment is associated with an increased rate of c-jun gene transcription. Transient expression assays with c-jun promoter fragments linked to the chloramphenicol acetyltransferase gene suggest that the PWM-induced increase in transcription is mediated by the AP-1 transcription factor complex. Moreover, treatment of T cells with actinomycin D to block further transcription before their culture with PWM suggests that the increase in c-jun gene expression by PWM is also regulated at least in part by a posttranscriptional mechanism. Cycloheximide does not alter c-jun mRNA induction by PWM. Finally, given that PWM induces B-cell differentiation in an interleukin-6 (IL-6)-mediated, T-cell-dependent manner, the relationship of c-jun and IL-6 gene expression in PWM-stimulated T cells was examined. The induction of IL-6 mRNA in T cells stimulated by PWM occurs after maximal induction of c-jun mRNA, at a time when the latter is no longer detectable. These findings suggest that PWM induces c-jun gene expression in T cells by a transcriptional and posttranscriptional mechanism and that AP-1 confers PWM inducibility of this gene. Because the IL-6 promoter has several potential transcriptional control elements, one of which is an AP-1-binding site, future experiments will evaluate the role of c-jun in the regulation of PWM-induced IL-6 synthesis by T cells.
Chauhan
D
D
Division of Tumor Immunology, Dana-Farber Cancer Institute, Boston, MA 02115.
Kharbanda
S M
SM
Rubin
E
E
Barut
B A
BA
Mohrbacher
A
A
Kufe
D W
DW
Anderson
K C
KC
D017252:CD3 Complex / Q000502:physiology; D015500:Chloramphenicol O-Acetyltransferase / Q000032:analysis; D005786:Gene Expression Regulation; D016762:Genes, fos; D016758:Genes, jun; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics; D011043:Pokeweed Mitogens; D012333:RNA, Messenger / Q000032:analysis; D013601:T-Lymphocytes / Q000378:metabolism*
D017252:CD3 Complex; D015850:Interleukin-6; D011043:Pokeweed Mitogens; D012333:RNA, Messenger; D015500:Chloramphenicol O-Acetyltransferase