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SUPERFAMILIES EMERGE. “Perhaps the most revolutionary finding to come from the cloning of the first steroid receptors was the surprising discovery that dozens of other evolutionarily related proteins exist.” https://lnkd.in/dXjCCgQ View in LinkedIn

STIMULANTS. "A 2006 study based on a 2002 survey indicated that 7 million Americans have misused these medicines. So this is a long-standing problem." http://www.forbes.com/sites/matthewherper/2012/06/10/the-questions-about-adhd-drugs-the-new-york-times-didnt-ask/#dddf7982f07a View in LinkedIn

GENE REGULATION. “As a result of this early work, transcriptional regulation by hormone-receptor complexes was shown to be a fundamental process embedded in the circuitry of extracellular signal transduction by lipophilic endocrine hormones and vitamins.” https://lnkd.in/dXjCCgQ View in LinkedIn

SO ENDS this lovely 2014 review of the historical highpoints in nuclear receptor discoveries. Mostly driven by the development of powerful methods, including gene isolation and reverse transfection, these led the way to big concepts that allowed significant discoveries to be made by shining their light into the darkness of the cell. This story, especially the Endogenous opioid superfamily, is one of the most endearing histories in biochemistry. View in LinkedIn

KNOCKOUT EXPERIMENTS. “Importantly, access to the cDNAs enabled key experiments needed to test protein function, including mutagenesis of the receptor's primary structure to assess the importance of specific amino acids and characterization of the nucleotide code within the target gene’s promoter that allows gene-specific expression.” https://lnkd.in/dXjCCgQ View in LinkedIn

DRUG DISCOVERY TARGETS. “Orphan nuclear receptors have now transitioned through the tipping point as therapeutic targets in the treatment of human disease.” https://lnkd.in/dXjCCgQ View in LinkedIn

TRANSFORMATIVE CONCEPT. “We refer to the discovery of heterodimerization as the “RXR Big Bang” because its explosive impact gave rise to a wave of discovery, including entirely new physiologic signaling pathways.” (RXR = retinoid receptor). https://lnkd.in/dXjCCgQ View in LinkedIn

SECOND BIG CONCEPT UNLEASHED. “Second, it led to the discovery of RXR heterodimerization with these adopted orphan receptors, thereby defining a novel feature of multiple intertwined signaling pathways.” (RXR = retinoid receptor). https://lnkd.in/dXjCCgQ View in LinkedIn

FIRST BIG CONCEPT UNLEASHED. “The discovery of RXR and its ligand resulted in the genesis of two prodigious concepts in the nuclear receptor field. First, in revealing the existence of a previously unknown signaling pathway, it provided a proof of principle that precipitated a wave of research aimed at linking other orphan receptors to specific ligands.” (RXR = retinoid receptor). https://lnkd.in/dXjCCgQ View in LinkedIn

LOW AFFINITY TARGETS. “A major role of the receptors for these lipid-derived ligands was to maintain the homeostasis of the ligands themselves. Thus, the natural ligands being identified turned out to be predictive hallmarks of the physiologic pathways being regulated by their cognate receptors.” https://lnkd.in/dXjCCgQ View in LinkedIn