Nuclear Receptors Flashcards
What is in the steroid receptor family (4)?
GR = glucocorticoid receptor
MR = mineralocorticoids
AR = androgen receptor
PR = progesterone receptor
What is in the thyroid receptor family (6)?
TR = thyroid hormone receptor
ER = estrogen receptor
RAR = retinoic acid receptor
RXR = retinoic X receptor
PPAR = peroxisome proliferator-activated receptor
VDR = vitamin D receptor
Where are steroid vs thyroid receptors stored?
Steroid receptors are stored in the cytoplasm (stabilized by HSPs), thyroid family receptors are stored in the nucleus
How does steroid receptor signaling work?
Hormones diffuse or transported across the membrane, cytoplasmic proteins may bind the hormone receptor (HSP), the receptor in the nucleus already bound to DNA repressing/activating, then binds hormones and activates/repress transcription
What does hormone binding do to HSP?
It releases HSP from receptor, which exposes the nuclear localization signal, dimerization of the receptor occurs, then the hormone receptor complex is transported into the nucleus, where it binds to HRE and activates/represses transcription
What is the function of amino terminal domain?
Involved in ligand-independent transactivation. AF-1 (activation function one) subdomain highly variable in length and sequence – don’t need ligand to activate transcription
What is the function of the DNA binding domain?
DNA binding, dimerization, highly homologous, basic region with two zinc fingers
What is the function of the ligand binding domain?
Hetero- and homo- dimerization, ligand binding, ligand-dependent transactivation, nuclear translocation, association with HSP
What do mutations in the LBD of TR cause?
Disease with resistance to TH, attention deficit to severe brain retardation
What is different about the ER?
It is in the thyroid receptor family by sequence homology, but it is a steroid and ER binds to HSP, but is more in the nucleus than steroid receptor family members
How many zinc ions per receptor?
2 zinc ions/receptor
What are the functions of zinc?
DNA binding and receptor dimerization, important in maintaining shape of the receptor
