ESRR - estrogen related receptor | Elisa - Clia - Antibody - Protein

Background

Estrogen-Related Receptors (ESRRs) are a group of orphan nuclear receptors that share structural similarity with estrogen receptors (ERs) but do not bind to estrogen. Despite this, they are involved in the regulation of a wide range of biological processes similar to those governed by ERs, such as energy metabolism, mitochondrial function, and cell proliferation. ESRRs are considered orphan receptors because their endogenous ligands are not yet identified. These receptors are significant in maintaining metabolic homeostasis and have been implicated in various diseases, including cancer, metabolic disorders, and cardiovascular diseases.

Protein Structure

ESRRs have a modular structure typical of nuclear receptors, comprising several distinct domains:

• N-terminal Domain (NTD): Contains the activation function-1 (AF-1) region, responsible for ligand-independent transcriptional activation.
• DNA-binding Domain (DBD): Features two zinc finger motifs that facilitate the binding to specific DNA sequences known as estrogen-related response elements (ERREs).
• Hinge Region: Provides structural flexibility and contains nuclear localization signals that direct the receptor to the nucleus.
• Ligand-binding Domain (LBD): Despite the lack of identified endogenous ligands, this domain is crucial for dimerization and interaction with co-regulators, contributing to the receptor's transcriptional activity.

Classification and Subtypes

There are three main members of the ESRR family:

• ESRRA (ERRα): Highly expressed in tissues with high energy demands, such as the heart, skeletal muscle, and brown adipose tissue. ERRα is a key regulator of mitochondrial biogenesis and oxidative metabolism.
• ESRRB (ERRβ): Plays essential roles in embryonic development and the maintenance of pluripotency in stem cells.
• ESRRG (ERRγ): Predominantly expressed in the brain, kidney, and liver, and is involved in the regulation of metabolic processes and energy homeostasis.

Function and Biological Significance

• Energy Metabolism: ESRRs regulate genes involved in mitochondrial function, fatty acid oxidation, and oxidative phosphorylation, thus playing a crucial role in energy homeostasis.
• Development and Differentiation: These receptors are involved in embryonic development, cell differentiation, and the maintenance of stem cell pluripotency.
• Cancer: ESRRs are implicated in the progression of various cancers, including breast, prostate, and ovarian cancers, through their role in cellular metabolism and proliferation.
• Cardiovascular Health: By regulating energy metabolism in the heart and blood vessels, ESRRs contribute to cardiovascular health and function.

Clinical Issues

• Cancer: The expression and activity of ESRRs in cancer cells make them potential targets for cancer therapy. ERRα, in particular, has been associated with poor prognosis in breast cancer.
• Metabolic Disorders: Dysregulation of ESRR activity is linked to metabolic disorders such as obesity and type 2 diabetes due to their role in regulating energy expenditure and glucose metabolism.
• Cardiovascular Diseases: Given their role in cardiac energy metabolism, ESRRs are being explored as therapeutic targets for heart failure and other cardiovascular diseases.

Summary

Estrogen-Related Receptors (ESRRs) are a family of orphan nuclear receptors structurally related to estrogen receptors but do not bind estrogen. They are critical regulators of energy metabolism, mitochondrial function, and cellular proliferation. ESRRs have three main subtypes—ERRα, ERRβ, and ERRγ—each with distinct tissue distribution and functions. These receptors are implicated in various physiological processes and diseases, including cancer, metabolic disorders, and cardiovascular diseases. Understanding their structure and function is essential for developing targeted therapies for these conditions.