Androgen receptor: Difference between revisions

Line 36:

===DNA-Binding dependent actions of the AR===

'''[[Image:Translocation.jpg | thumb | upright=1.5 | Tan et al. <ref name="Structure" /> ]]'''

'''[[Image:Translocation.jpg | thumb | upright=1.5 | Reproduced from Tan et al. <ref name="Structure" /> ]]'''

In the absence of ligand, the AR is in the cytoplasm and associated with heat-shock and other chaperone proteins. Testosterone is converted into DHT by 5α-reductase, with higher affinity to bind the receptor. When DHT binds AR, it displaces heat shock proteins, drives the interaction between the N- and C-terminal, and binds importin-α to translocate the ligand/AR complex into the nucleus.

Line 44:

===Non-DNA Binding dependent actions of the AR===

It has been shown that the androgen/AR complex activates 2nd messenger pathways including ERK, Akt and MAPK and ~~that~~ it interferes with several key proteins including forkhead box protein A1 (FOXA1), PI3K and receptor tyrosine kinases~~, including ERBB2 and ERBB3~~. These effects occur within seconds to minutes of androgen treatment <ref name="Bench to Bedside" /><ref>PMID: 28301631</ref>.

It has been shown that the androgen/AR complex activates 2nd messenger pathways including ERK, Akt and MAPK, and it also interferes with several key proteins including forkhead box protein A1 (FOXA1), PI3K and receptor tyrosine kinases. These effects occur within seconds to minutes of androgen treatment <ref name="Bench to Bedside" /><ref>PMID: 28301631</ref>.

There are studies ~~that suggest~~ that some of the non-DNA binding-dependent actions of androgens are mediated via the activation of membrane-bound protein receptors. For instance, the iron-regulated transporter-like protein 9 (ZIP9) mediates the androgen-induced apoptosis of ovarian follicle cells, prostate and breast cancer cells <ref name="Bench to Bedside" />.

Although the physiological significance of the non-DNA binding-dependent actions of the AR is not yet fully defined, it has been proposed ~~that~~ they may oppose the DNA binding-dependent actions and serve as a brake to fine-tune androgen action in target tissues <ref name="Bench to Bedside" />.

There are studies suggesting that some of the non-DNA binding-dependent actions of androgens are mediated via the activation of membrane-bound protein receptors. For instance, the iron-regulated transporter-like protein 9 (ZIP9) mediates the androgen-induced apoptosis of ovarian follicle cells, prostate and breast cancer cells <ref name="Bench to Bedside" />.

Although the physiological significance of the non-DNA binding-dependent actions of the AR is not yet fully defined, it has been proposed they may oppose the DNA binding-dependent actions and serve as a brake to fine-tune androgen action in target tissues <ref name="Bench to Bedside" />.

===Ligand-Independent actions of the AR===

Androgen receptor: Difference between revisions

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@@ Line 36: / Line 36: @@
 ===DNA-Binding dependent actions of the AR===
-'''[[Image:Translocation.jpg | thumb | upright=1.5 | Tan et al. <ref name="Structure" /> ]]'''
+'''[[Image:Translocation.jpg | thumb | upright=1.5 | Reproduced from Tan et al. <ref name="Structure" /> ]]'''
 In the absence of ligand, the AR is in the cytoplasm and associated with heat-shock and other chaperone proteins. Testosterone is converted into DHT by 5α-reductase, with higher affinity to bind the receptor. When DHT binds AR, it displaces heat shock proteins, drives the interaction between the N- and C-terminal, and binds importin-α to translocate the ligand/AR complex into the nucleus.
@@ Line 44: / Line 44: @@
 ===Non-DNA Binding dependent actions of the AR===
-It has been shown that the androgen/AR complex activates 2nd messenger pathways including ERK, Akt and MAPK and that it interferes with several key proteins including forkhead box protein A1 (FOXA1), PI3K and receptor tyrosine kinases, including ERBB2 and ERBB3. These effects occur within seconds to minutes of androgen treatment <ref name="Bench to Bedside" /><ref>PMID: 28301631</ref>.
+It has been shown that the androgen/AR complex activates 2nd messenger pathways including ERK, Akt and MAPK, and it also interferes with several key proteins including forkhead box protein A1 (FOXA1), PI3K and receptor tyrosine kinases. These effects occur within seconds to minutes of androgen treatment <ref name="Bench to Bedside" /><ref>PMID: 28301631</ref>.
-There are studies that suggest that some of the non-DNA binding-dependent actions of androgens are mediated via the activation of membrane-bound protein receptors. For instance, the iron-regulated transporter-like protein 9 (ZIP9) mediates the androgen-induced apoptosis of ovarian follicle cells, prostate and breast cancer cells <ref name="Bench to Bedside" />.
-Although the physiological significance of the non-DNA binding-dependent actions of the AR is not yet fully defined, it has been proposed that they may oppose the DNA binding-dependent actions and serve as a brake to fine-tune androgen action in target tissues <ref name="Bench to Bedside" />.
+There are studies suggesting that some of the non-DNA binding-dependent actions of androgens are mediated via the activation of membrane-bound protein receptors. For instance, the iron-regulated transporter-like protein 9 (ZIP9) mediates the androgen-induced apoptosis of ovarian follicle cells, prostate and breast cancer cells <ref name="Bench to Bedside" />.
+Although the physiological significance of the non-DNA binding-dependent actions of the AR is not yet fully defined, it has been proposed they may oppose the DNA binding-dependent actions and serve as a brake to fine-tune androgen action in target tissues <ref name="Bench to Bedside" />.
 ===Ligand-Independent actions of the AR===