title: Nutritional conditions regulate transcriptional activity of SF-1 by controlling sumoylation and ubiquitination.
abstract: 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.
authors.affiliation: Departments of Pharmacology and Internal Medicine, Division of Hypothalamic Research, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
authors.forename: Jiwon
authors.initials: J
authors.lastname: Lee
authors.affiliation: Departments of Pharmacology and Global Medical Science, Institute of Lifestyle Medicine and Nuclear Receptor Research Consortium, Wonju College of Medicine, Yonsei University, Wonju, 26426, South Korea.
authors.forename: Dong Joo
authors.initials: DJ
authors.lastname: Yang
authors.affiliation: Departments of Pharmacology and Internal Medicine, Division of Hypothalamic Research, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
authors.forename: Syann
authors.initials: S
authors.lastname: Lee
authors.affiliation: Endocrine Oncology Program, Center for Organogenesis, University of Michigan Health System, Ann Arbor, Michigan 48109, USA.
authors.forename: Gary D
authors.initials: GD
authors.lastname: Hammer
authors.affiliation: Departments of Pharmacology and Global Medical Science, Institute of Lifestyle Medicine and Nuclear Receptor Research Consortium, Wonju College of Medicine, Yonsei University, Wonju, 26426, South Korea.
authors.forename: Ki Woo
authors.initials: KW
authors.lastname: Kim
authors.affiliation: Departments of Pharmacology and Internal Medicine, Division of Hypothalamic Research, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
authors.forename: Joel K
authors.initials: JK
authors.lastname: Elmquist
mesh_terms: D000818:Animals; D002460:Cell Line; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology; D008954:Models, Biological; D055550:Protein Stability; D059748:Proteolysis; D015398:Signal Transduction; D054339:Steroidogenic Factor 1 / Q000378:metabolism*; D058207:Sumoylation / Q000187:drug effects; D015533:Transcriptional Activation; D054875:Ubiquitination / Q000187:drug effects
chemical_list: D007328:Insulin; D054339:Steroidogenic Factor 1