By Chung Bon-chu, Hu Meng-Chun (auth.), Chawnshang Chang (eds.)
Androgen Receptors is the main entire and recent quantity at the subject, together with discussions of the fundamental mechanisms of androgen-androgen receptor activities, their roles within the androgen-related ailments, and their capability scientific applications.
Key subject matters coated comprise:
-The discovery and cloning of the androgen receptor;
-Androgen receptor coregulators;
-Androgen comparable genes and their consensus DNA reaction components;
-Basic mechanism of motion together with useful analyses, mobile localization and phosphorylation stories;
-Cross-talk to different sign transduction platforms;
-The contemporary connections of androgens to women's illnesses, reminiscent of osteoporosis and ovarian cancer.
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Extra resources for Androgens and Androgen Receptor: Mechanisms, Functions, and Clinical Applications
The biological importance ofthe AR-A isoform is not c1ear and for the purposes of this chapter only the full-Iength AR isoform will be discussed. The AR shares the overall domain structure that typifies the members ofthe nuclear receptor superfamily. The AR protein can be divided into four functional domains: the NH 2-terminal transactivation domain (or AlB domain), the DBD, the hinge region, and the LBD. Two transcriptional activation functions have been identified on the basis of deletion and mutational analyses.
The activated receptor complex mediates the phosphorylation of Smad 2 and Smad 3, enabling them to heterodimerize with Smad 4 to form a Smad complex that binds to a specific response element to activate transcription of target genes (Massague and Chen, 2000 ; Massague and Wotton , 2000). , 1996). Restoration of TGFß signaling in LNCaP cells by stable transfection of the TGFß-RII results in reduced tumorigenicity in nude mice associated with enhanced apoptosis (Guo and Kyprianou, 1999). Smad 3 has been shown to interact with AR.
Coregulators, including ARA 70 (70) and ARA55 (55), bind to the AR dimer. In the case ofARA 70, the AR-ARA 70 interaction stabilizes the bound ligand. Phosphorylation ofAR in response to activation of receptor tyrosine kinases (RTK) such as Her2 can increase the ability ofAR to recruit the coactivators ARA 70 and ARA55 (bold arrows). 30 Upon ligand binding, the chaperone complex dissociates from the receptor as a result of the altered conformation of the ligand bound LBD (Pratt and Toft, 1997) .
Androgens and Androgen Receptor: Mechanisms, Functions, and Clinical Applications by Chung Bon-chu, Hu Meng-Chun (auth.), Chawnshang Chang (eds.)