Steroidogenic factor 1 (SF-1) is a transcription factor expressed in the ventral medial nucleus of the hypothalamus that regulates energy homeostasis. However, the molecular mechanisms of SF-1 in the control of energy balance are largely unknown. Here, we show that nutritional conditions, such as the presence or absence of serum, affect SF-1 action. Serum starvation significantly decreased hypothalamic SF-1 levels by promoting ubiquitin-dependent degradation, and sumoylation was required for this process. SF-1 transcriptional activity was also differentially regulated by nutritional status. Under normal conditions, the transcriptional activity of hypothalamic SF-1 was activated by SUMO, but this was attenuated during starvation. Taken together, these results indicate that sumoylation and ubiquitination play crucial roles in the regulation of SF-1 function and that these effects are dependent on nutritional conditions, further supporting the importance of SF-1 in the control of energy homeostasis.
Bibliographical noteFunding Information:
We thank Dr. Hongtao Yu (UT Southwestern Medical Center) for providing GFP-SUMO constructs. This work was supported by NIH grants R01DK088423, R37DK053301 (to J.K.E) and by National Research Foundation NRF-2013R1A1A1007693 and Yonsei University Wonju College of Medicine YUWCM-2013-53 (to K.W.K). J.L. is supported by a Green Center Trainee Fellowship from UT Southwestern Medical Center and D.J.Y is supported by Global Ph.D. Fellowship (NRF-2015H1A2A1032009).
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