Regulation of c-jun gene expression in human T lymphocytes
D Chauhan, SM Kharbanda, E Rubin, BA Barut, A Mohrbacher, DW Kufe and KC Anderson
Division of Tumor Immunology, Dana-Farber Cancer Institute, Boston, MA
02115.
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.
Volume 81,
Issue 6,
pp. 1540-1548,
03/15/1993
Copyright © 1993 by The American Society of Hematology
