Nuclear Hormone Receptor
Nuclear hormone receptors refer to the targets of hormones in the nucleus and belong to nuclear receptors. Nuclear receptors are a class of ligand-dependent transcription factors that are widely distributed in organisms. They have many members and form a large family. They can be divided into three categories: steroid hormone receptors, non-steroid hormone receptors and orphan nuclear receptors. Steroid hormone receptors and non-steroid hormone receptors are collectively referred to as nuclear hormone receptors. In other words, the vast majority of nuclear receptors are hormone receptors. Unlike receptors on the cell surface, these receptors are only found in metazoans (such as nematodes, insects, and vertebrates) and are mostly trans-acting factors. When the receptor is combined with the corresponding hormone, it can combine with the cis-acting element of DNA to regulate gene transcription, thereby playing an important role in the body's growth and development, metabolism, cell differentiation and many physiological processes in the body. Dysfunction of such receptors will lead to a range of diseases such as cancer, infertility, obesity, diabetes.
1. The Structure of Nuclear Hormone Receptor
As mentioned before, nuclear hormone receptors are contained in nuclear receptors, and the typical structure of nuclear receptors is divided into six parts, namely A, B, C, D, E and F regions. N-terminal (A/B region), highly variable, contains at least one ligand-independent transcriptional activation domain (AF1) that is itself active and can receive ligand-independent cis-activation. The C region is the most conserved region in the nuclear receptor superfamily, namely the DNA binding region (DBD), which is the domain that determines the binding activity of receptors to DNA, and is also a characteristic region of nuclear receptors. In the DNA binding region (C region) and the ligand binding region (E region), there is a short and unconserved structure called the hinge region (D region), which mainly acts as a hinge in the C region and the E region, and contains a nuclear localization signal peptide (NLS). The E region, also known as the ligand-binding region (LBD), is the largest domain in nuclear receptors, and its sequence is highly conserved to fully ensure the recognition of selective ligands. This region contains a ligand-dependent transcriptional activation domain (AF2), which is very important in transcriptional regulation. Some nuclear receptors also contain an F region. The sequence of the F region is highly variable outside the C-terminus of the E region, and its structure and function are still unclear.
Figure 1. The Structure of Nuclear Receptor
2. The Classification of Nuclear Hormone Receptor
Nuclear hormone receptors can be divided into steroid hormone receptors and non-steroid hormone receptors according to the type of hormone they bind.
Steroid hormone receptors, also known as type I nuclear receptors, include estrogen receptors, androgen receptors, progesterone receptors, and glucocorticoid receptors. Steroid hormone ligands of this receptor subgroup bind to steroid-binding globulin after transport from their respective endocrine glands through the bloodstream. After such receptors bind to ligands, the receptors are transported to the nucleus to form homodimers, which together with other cofactors regulate transcription and output signals. Nonsteroidal hormone receptors, also known as type II nuclear receptors, include thyroid hormone receptors, retinoic acid receptors, vitamin D receptors, and PPARγ. Upon ligand binding, these receptors can heterodimerize the retinoid X receptor (RXR), which together with other cofactors regulate transcription and output signals.
3. Popular Targets Related Nuclear Hormone Receptor
CUSABIO has listed some popular targets related nuclear hormone receptor. Click on the corresponding target to view all the reagents related to the target.