USF2 inhibits C/EBP-mediated transcriptional regulation of the RIIbeta subunit of cAMP-dependent protein kinase.

BACKGROUND

Cyclic AMP-dependent protein kinase (PKA) plays a central role in regulation of energy metabolism. Upon stimulation of testicular Sertoli cells by follicle stimulating hormone (FSH), glycolysis is activated to increase the production of nutrients for the germ cells, and a new regulatory subunit of cAMP-dependent protein kinase, RIIbeta, is induced. We have previously shown that production of the transcription factor C/EBPbeta is rapidly increased by FSH and cAMP in primary Sertoli cell cultures, and that C/EBPbeta induces the RIIbeta promoter.

RESULTS

In this work we show that USF1, USF2 and truncated USF isoforms bind to a conserved E-box in the RIIbeta gene. Interestingly, overexpression of USF2, but not USF1, led to inhibition of both cAMP- and C/EBPbeta-mediated induction of RIIbeta. Furthermore, Western blots show that a novel USF1 isoform is induced by cAMP in Sertoli cells.

CONCLUSIONS

These results indicate that the expression of various USF isoforms may be regulated by cAMP, and that the interplay between USF and C/EBPbeta is important for cAMP-mediated regulation of RIIbeta expression. The counteracting effects of USF2 and C/EBPbeta observed on the RIIbeta promoter is in accordance with the hypothesis that C/EBP and USF play opposite roles in regulation of glucose metabolism.