Lecture 8 Flashcards
What are nuclear hormone receptors?
aka intracellular receptors. The most direct connection of all between extracellular signals and the control of transcription. These are single step signal transduction systems, with one protein both binding a hormone of extracellular origin, and acting as a regulator of gene transcription.
Defects in NHR’s can cause diseases!!
Common functions of NHRs
They are sufficiently hydrophobic to diffuse across PM and nuclear membrane, interact with an intracellular receptor.
The hormone enters cell and binds a previously inactive receptor, turning it on as a transcription factor. Binds to DNA sites near promotors. This ACTIVATES or REPRESSES transcription of the target gene.
Structure: a central DNA binding domain, and a C-terminal hormone binding domain.
What’s a ligand?
A substance that forms a complex with a biomolecule to serve a purpose. Often changes the conformation of the molecule.
NHR Ligands
Lipophilic (Fat-Liking) substances such as endogenous hormones, vitamins A and D, and xenobiotic endocrine disruptors.
Often referred to as orphan receptors, or proteins with unknown hormone specificities.
What are mechanisms by which nuclear hormone receptors regulate transcription?
Coactivators: Acetylate histones, increasing accessibility for the transcriptional machinery. Also creates a
“histone code” that can control the ability of other proteins to bind to the chromatin.
Corepressors: remove acetate groups from histones. making the chromatin more condensed, change the histone code, and render the chromatin less able to be transcribed.
Homo- and hetero-dimers
A homo-dimer would be formed by two identical molecules (a process called homodimerization). Example, NHR and NHR.
A hetero-dimer would be formed by two different macromolecules (called heterodimerization). Example, NHR and something else.
Xenobiotic response
A xenobiotic is a foreign chemical substance found within an organism that is not normally naturally produced by or expected to be present within that organism.
Orphan Receptors
Can determine physiological and phenotypical outcomes like gender, size, etc.
Can be ligand independent transcription factors.
Are often Lipid intermediates.
