Dahle Maria Krudtaa, Taskén Kjetil, Taskén Kristin Austlid
Department of Medical Biochemistry, Institute of Basic Medical Sciences, University of Oslo, N-0317 Oslo, Norway.
BMC Mol Biol. 2002 Jun 21;3:10. doi: 10.1186/1471-2199-3-10.
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.
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.
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.
环磷酸腺苷依赖性蛋白激酶（PKA）在能量代谢调节中起核心作用。在卵泡刺激素（FSH）刺激睾丸支持细胞后，糖酵解被激活，以增加生殖细胞营养物质的产生，并且诱导了一种新的环磷酸腺苷依赖性蛋白激酶调节亚基RIIβ。我们之前已经表明，在原代支持细胞培养物中，转录因子C/EBPβ的产生会被FSH和环磷酸腺苷迅速增加，并且C/EBPβ会诱导RIIβ启动子。
在这项研究中，我们发现USF1、USF2和截短的USF异构体与RIIβ基因中的一个保守E盒结合。有趣的是，过表达USF2而非USF1会导致抑制环磷酸腺苷和C/EBPβ介导的RIIβ诱导。此外，蛋白质免疫印迹显示，支持细胞中环磷酸腺苷会诱导一种新的USF1异构体。
这些结果表明，各种USF异构体的表达可能受环磷酸腺苷调节，并且USF和C/EBPβ之间的相互作用对于环磷酸腺苷介导的RIIβ表达调节很重要。在RIIβ启动子上观察到的USF2和C/EBPβ的拮抗作用符合C/EBP和USF在葡萄糖代谢调节中起相反作用的假说。
