Nuclear Receptor/Transcription Factor

Transcription factors are involved in a large number of human diseases such as cancers. With the exception of ligand-inducible nuclear receptors, transcription factors were considered as “undruggable” targets. Advances knowledge of these transcription factors, in terms of structure, function (expression, degradation, interaction with co-factors and other proteins) and the dynamics of their mode of binding to DNA has changed this postulate and paved the way for new therapies targeted against transcription factors. Nuclear receptors are a family of ligand-regulated transcription factors that are activated by steroid hormones, such as estrogen and progesterone, and various other lipid-soluble signals, including retinoic acid, oxysterols, and thyroid hormone. 
Unlike most intercellular messengers, the ligands can cross the plasma membrane and directly interact with nuclear receptors inside the cell, rather than having to act via cell surface receptors. Once activated, nuclear receptors directly regulate transcription of genes that control a wide variety of biological processes, including cell proliferation, development, metabolism, and reproduction. Although nuclear receptors primarily function as transcription factors, some have also been found to regulate cellular functions within the cytoplasm. For example, estrogens act through the estrogen receptor in the cytoplasm of endothelial cells to rapidly activate signaling pathways that control vascular tone and endothelial cell migration.

References:

1.Takaomi Sanda.Molecules. 2018 Jun; 23(6): 1479.  
2.Richard Sever1 and Christopher K. Glass.Cold Spring Harb Perspect Biol. 2013 Mar; 5(3): a016709.