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Printable Handouts
Navigable Slide Index
- Introduction
- Mechanisms of androgen action
- Androgen receptor (1)
- Testosterone and dihydrotestosterone bind AR
- Phenotypic effect of mutation in AR receptor
- Mutations in the androgen receptor
- AR transcriptional activity and DHT/ testosterone
- Testosterone dissociates faster than DHT
- [3H]R1881 dissociation from AR, AR507-920
- Androgen receptor N/C interaction
- Androgen receptor (2)
- A model of the FXXLF motif
- Charge polarity of FXXLF motifs binding AR
- AR ligand binding domain
- AR20-30 RGAFQNLFQSV bound to AF2 in AR
- AR FXXLF motif
- Androgen-induced N/C interaction
- Requirement for AR N/C interaction and TIF2
- Androgen dependent stabilization of AR
- AR N/C interaction
- The interaction of the motifs with the AR LBD
- AR FXXLF - SRC/p160 LXXLL competition
- SRC/p160 - nuclear receptor coactivators family
- LXXLL motif forms amphipathic alpha-helix
- Superimposed TIF2 LXXLL and AR FXXLF
- N/C interaction represses TIF2 recruitment
- Recruitment of nuclear receptor coregulators
- Melanoma antigen gene protein-11 (MAGE-11)
- Some of the features of MAGE-11
- Human MAGE-11
- Mammalian two hybrid interaction assay
- AR NH2-terminal FXXLF motif fragments
- FXXLF dependent AR - MAGE-11 interaction
- Overlapping AR FXXLF binding sites
- MAGE-11 specifically binds the AR FXXLF motif
- Colocalization of AR and MAGE-11 in COS cells
- Increased AR transactivation of PSA-Luc
- AR-AF2 activation by SRC/p160 coactivators
- AF1 and AF2 active in reproductive tract tissues
- Androgen insensitivity syndrome
- Phenotypic grades of androgen insensitivity
- AR-R1881-FXXLF
- Dissociation of [3H]R1881
- AR AIS mutations disrupt F27 binding to AF2
- AR AIS mutations disrupt F23 binding to AF2
- AR AIS mutation in ligand gateway
- Prostate cancer
- AR in BPH and recurrent prostate cancer (CaP)
- Mechanisms of prostate cancer progression
- Increased SRC/p160 coactivator levels in CaP
- Highly expressed cofactors in prostate cancer
- AR mutations in CaP increase AR activity
- Three gain-of-function AR mutations in CaP
- Summary
Topics Covered
- Mechanisms of androgen action
- Biological basis for androgen potency
- Androgen receptor FXXLF motif and N/C interaction
- Androgen receptor coactivator melanoma antigen gene protein-11
- Androgen receptor mutations in the androgen insensitivity syndrome and prostate cancer
- Mechanisms of prostate cancer progression to castration-recurrent disease
Links
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Talk Citation
Wilson, E. (2022, April 12). Understanding hormones: mechanisms of androgen receptor function in reproduction and cancer [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved December 22, 2024, from https://doi.org/10.69645/OSUR7861.Export Citation (RIS)
Publication History
Financial Disclosures
- Prof. Elizabeth Wilson has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.
Understanding hormones: mechanisms of androgen receptor function in reproduction and cancer
A selection of talks on Reproduction & Development
Transcript
Please wait while the transcript is being prepared...
0:00
My name is Elizabeth Wilson, I'm professor
of Pediatrics in Biochemistry at
the University of
North Carolina at Chapel Hill.
I've prepared this lecture entitled
"Mechanisms of Androgen Receptor Function
in Reproduction and Cancer".
There have been many exciting developments
in the field of nuclear receptors,
of which these steroid
receptors form a subset.
Studies on the androgen receptor
are particularly important in
relation to its function in terms
of this syndrome of androgen
insensitivity and also in prostate cancer.
0:34
This is a simplistic
diagram of androgen action.
In humans there is only one receptor for
androgens and
the two biologically active
androgens are testosterone,
shown here as T or
dihydrotestosterone or DHT.
Testosterone is the major circulating
form of androgen in the male,
and it's produced by the testes.
And then in peripheral tissues
testosterone is converted to
dihydrotestosterone, which
is a more active androgen.
Binding of either of these androgens
targets the receptor to the nucleus,
where then interacts with
specific DNA response elements.
The androgen receptor in the nucleus
acts as a docking site for
a number of interacting proteins.
These include co-regulatory proteins, the
most well known of which are the SRC or
steroid receptor coactivator, p160 family.
Then more than 50 interacting proteins and
also corepressors.
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