Daminozide, histone demethylase KDM2/7 subfamily inhibitor

Supplementary information

This supplementary information is collated from multiple sources and compiled automatically.

Estrogen Related Receptor Alpha (ERRα) also known as NR3B1 is a member of the nuclear receptor family. It is a protein involved in the transcriptional regulation of genes. ERRα has a molecular mass of approximately 51 kDa and is mainly expressed in tissues with high energy demands like skeletal muscle and heart tissue. This protein functions as a transcription factor modulating the expression of genes related to energy metabolism by binding to estrogen-related receptor response elements on DNA.

Biological function summary

ERRα plays a significant role in regulating energy homeostasis and mitochondrial biogenesis. ERRα does not require estrogen for activation differentiating it from other estrogen-related receptors. It often functions as part of a transcriptional complex interacting with coactivators such as PGC-1α. It helps in the expression of genes that manage oxidative phosphorylation and fatty acid metabolism highlighting its significance in energy balance regulation.

Pathways

The function of ERRα integrates mainly into the pathways controlling energy metabolism and mitochondrial function. It is intrinsically involved in the PPAR signaling pathway where it collaborates with peroxisome proliferator-activated receptors and the PGC-1 family of transcriptional coactivators to regulate genes associated with oxidative metabolism. ERRα influences the AMP-activated protein kinase (AMPK) pathway assisting in maintaining energy balance under varying nutritional states and promoting cellular energy efficiency.

ERRα has links with metabolic diseases and certain cancers. It's associated with metabolic disorders such as obesity as its regulation impacts energy expenditure and lipid metabolism. ERRα is also studied in the context of breast cancer where its expression correlates with tumor aggressiveness due to its role in energy metabolism remodeling in cancer cells. In breast cancer ERRα often interacts functionally with the HER2 pathway which is critical in the progression of some breast cancer subtypes.