Month: September 2022

STEROID RECEPTOR MODEL. “Comparison of the sequences revealed a conserved evolutionary template, and it also permitted the delineation of the structural and functional features that foreshadowed the emergence of a nuclear receptor superfamily.” https://lnkd.in/dXjCCgQ View in LinkedIn

THE TEMPLATE STRUCTURE. “Each sequence harbors DNA binding, ligand binding, and transactivation domains.” https://lnkd.in/dXjCCgQ 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

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

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

FUNCTIONS UNKNOWN. “Because the associated small-molecule ligands were unknown, they garnered the name “orphan” receptors.” https://lnkd.in/dXjCCgQ View in LinkedIn

CONSERVED AND LINEAGE-SPECIFIC. “Of further phylogenic significance, these orphan receptors were shown to be conserved throughout metazoan evolution, although it should be noted that nuclear receptors are absent in protozoans, fungi, and plants.” https://lnkd.in/dXjCCgQ View in LinkedIn

THE OUTLINES OF PATHWAYS. “That there were orphan receptors immediately suggested the existence of a host of previously unknown signaling pathways regulated by a myriad of undiscovered ligands.” https://lnkd.in/dXjCCgQ View in LinkedIn

THE NEED TO ID PATHWAYS. Now that the nuclear receptor pathways and functions needed elucidating, new fast screening methods had to be developed, since old methods were very slow and laborious. View in LinkedIn

OLD BRUTE FORCE METHODS. “In comparison, the classic endocrinology methods that led to the isolation of thyroid hormone in 1914 required 3.5 tons of bovine thyroid gland.” https://lnkd.in/dXjCCgQ View in LinkedIn