Steroid Hormone Receptor Signalling Flashcards
(21 cards)
What is special about steroid hormones
They are lipid soluble meaning they can enter the cell and bind to receptors inside the cell
What is special about cytoplasmic receptors
They directly control gene expression by going to the nucleus and binding dna
Then they recruit coactivators and corepressors
What are the transcription factors domains
DNA binding domain
Transactivation domain
Also could have ligand binding domain
What is the dna binding domain
It binds to specific dna sequences (response elements) in a gene promoter
Steroid hormone receptors have
DNA binding domains
This is why they’re diff from regular receptors since they are receptors and transcription factors
What is the transactivation domain
A part of the transcription factor/steroid hormone receptor that activates transcription
What is the ligand binding domain
A domain on the nuclear receptor to that ligands bind to activate it, then it can lead to nuclear translocation
(Moving the receptor to the nucleus)
What is an example of a steroid hormone receptor
Glucocorticoid receptor with its ligand cortisol which is a steroid hormone
Cortisol can pass through the membrane to bind to the Glucocorticoid receptor in the cytoplasm.
Then together they go into the nucleus and act as transcription factors for a gene
Before the receptors ligand is present, what is the steroid hormone receptor interacting with
It interacts with a chaperone protien to prevent inappropriate interactions of the receptor with different protiens
Once the ligand binds, the chaperone falls off
What is an example of a chaperone protien
The HSP90
(Heat shock protien 90)
What does the glucocorticoid receptor bind to
The glucocorticoid response element (GRE) which is palindromic (both dna strand have same 5’ to 3’ sequence)
What type of protien is the GC receptor
A zinc finger protien
What is a zinc finger protien
The receptor has zinc ions that are in between two cysteines and two histidines
These form aplha helices that act as fingers to project into the major groove of the dna
How is transcription activated through the use of steroid hormone receptors
To activate the the GC receptor, cortisol binds to it then it binds to dna through the zinc finger motif
Then the active GC receptor binds to the dna and recruits the coactivator CBP
CBP is a histone acetyltransferase which acetylates the histones of the nucleosome
What happens once the histone in transcription activation are acetylated
The acetylated histones recruit SW1 / SNF chromatin remodeling complex
The SW1 / SNF disrupt the dna interactions with the nucelosome by sliding the nucleosome of bumping them off the dna
After SW1 / SNF displaces the histone what happens
The transcriptional machinery and rna pol 11 can bind to the dna for transcription
Steroid receptors can be
Transcription repressor
Transcription activators
How is transcriptional repression done
The repressor (could be a steroid receptor) recruits a corepressor that recruits a HDAC
Then the histones in that area are deacetylated and transcription is repressed
Further recruitment of methyl transferase happens
In transcriptional repression what happens after the methyl transferase is recruited
It methylated lysine 9 of histone 3 (H3K9)
This leads to the inactive chromatin and silence of genes
What are examples of corepressors
NCoR and SMRT
How can steroid hormone receptors reprogram cells
They act as transcription factor to repress or activate transcription
So it take for example a neural stem cell to then reprogram it to a mammary stem cell
