fig1

Resistance to second generation antiandrogens in prostate cancer: pathways and mechanisms

Figure 1. The androgen-androgen receptor signaling pathway. A: The androgen receptor gene resides on the long arm of X chromosome (locus Xq11-Xq12). Upon transcription it produces mRNA containing 8 exons interrupted by introns which codes for the AR protein made up of 919 amino acids. AR protein contains several functional domains such as N-terminal domain (NTD), DNA binding domain (DBD) and ligand binding domain (LBD); B: Ligand binding domain of androgen receptor in complex with its ligand 5-α-dihydrotestosterone (5ADHT). The crystal structure of the androgen receptor ligand binding domain in complex with 5-alpha dihydrotestosterone (PDB ID 1T7T with resolution 1.70Å) was downloaded from RCSB protein databank. The PyMOL molecular visualization system was used to represent the protein-ligand complex in cartoon-sticks form; C: General mechanism of AR signaling. Testosterone diffuses into the cells and gets converted into dihydrotestosterone (DHT) via the action 5-α-reductase (5-a-R). DHT binds to the ligand binding pocket of androgen receptor (AR) and promotes its dissociation from the heat shock protein (HSP). Free AR then translocate into the nucleus and binds to androgen receptor element (ARE) present in the promoter region of AR responsive genes. At the promoter AR recruits components of basal transcriptional machinery such as TATA binding protein (TBP), transcription factor IIF (TFIIF), and cAMP responsive element binding protein (CRBP) which ensures the transcription of AR responsive genes

Cancer Drug Resistance
ISSN 2578-532X (Online)

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