Interleukin 1 activation of the AP-1 transcription complex in murine T cells is regulated at the level of Jun B protein accumulation.
We have examined the regulation of the AP-1 DNA transcription complex during T cell activation in response to interleukin 1 (IL-1) and phorbol ester (TPA) treatment of the IL-1 responsive murine thymoma T cell line, EL4 6.1 C 10. IL-1 synergistically enhances the stimulatory effect of TPA on AP-1-mediated gene expression in this cell line. To elucidate the mechanism(s) by which IL-1 enhances AP-1-mediated gene expression, we examined the effect of IL-1 on the synthesis and turnover of Jun B, the member of the jun gene family that is present in AP-1 complexes in EL4 cells. We found that IL-1 + TPA-treated cells contain significantly higher Jun B protein levels than cells treated with TPA alone. IL-1 promotes the prolonged accumulation of Jun B, whereas the cellular content of Jun B decreases dramatically after 6 hr in cells treated with only TPA. IL-1 enhancement of Jun B protein levels is not the result of a change in the turnover rate of the Jun B protein, but rather results from the maintenance of sufficient jun B mRNA to support continued accumulation of newly synthesized protein. In addition to Jun B, we found that the T cell AP-1 complex contains the Fra-1 protein, a member of the fos gene family. Although IL-1 dramatically increases Jun B accumulation, it does not enhance TPA-induced Fra-1 protein levels in EL4 cells. Thus, the stimulation of AP-1-mediated gene expression by IL-1 in EL4 cells is due to the promotion of Jun B protein accumulation that, in turn, facilitates Jun B heterodimerization with TPA-induced Fra-1 protein, thereby forming an active AP-1 complex.
Brooks
J W
JW
Department of Microbiology and Immunology, Wake Forest University Medical Center, Winston-Salem, NC 27157, USA.
Yoza
B K
BK
Mizel
S B
SB
D000818:Animals; D015972:Gene Expression Regulation, Neoplastic; D007375:Interleukin-1 / Q000378:metabolism / Q000494:pharmacology*; D008213:Lymphocyte Activation; D051379:Mice; D016759:Oncogene Protein p65(gag-jun) / Q000096:biosynthesis*; D010766:Phosphorylation; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D013945:Thymoma / Q000276:immunology / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D007375:Interleukin-1; D016759:Oncogene Protein p65(gag-jun); D018808:Transcription Factor AP-1