Mol Cell: The implicationofous effects of androgen receptor structure on prostate cancer.

!---- androgen receptor (AR) is a transcription factor activated by androgens that plays a key role in the growth and development of males and females, including skeletal muscle, heart, nervous system, and reproductive systems, which control the development and growth of male signs, while regulating male and female hair growth and sexual impulses, and more importantly, androgen receptors (AR) are considered key starting proteins for the development and development of prostate cancer.prostate cancer is the second leading cause of death in men, and prostate cancer is triggered by abnormal regulation of genes by androgen receptors (AR), and we need to better understand the mechanism of androgen receptors (AR) in order to effectively treat this type of cancer.AR is a hormonal nuclear receptor super family, and all similar steroid receptors consist of three basic components: highly specificN-terminal domain (NTD), conservative DNA binding domain (DBD) in the middle, and ligand binding domain (LBD) at the c-side.previous studies have shown that androgen receptors (ARs) combine testosterone to dissose and form dipolymers from the heat shock protein, and enter the nucleus to bind to DNA, further collecting co-activation factors and other active complexes that promote protein formation, which in turn regulates the specific genes necessary for growth and development.how the regions within the AR dipolymer interact and how to collect other co-activators (co-activator) and then regulate gene expression remains unknown, so studying the three-dimensional structure of the AR dipolymer and its active complex will help us understand the mechanism of androgen receptors (AR) in cancer.To better understand the mechanisms of androgen receptors (AR) in cancer, on July 14, 2020, a team of researchers at Baylor College of Medicine, Usain O'Malley, and a team of assistant professors from Wang Wei (co-authored by Dr. Yu Xinyi and Yip) published an article in the journal Molecular Insights of The R. Full-Length Androgen Receptor Coactivator Complexes, a structural analysis and biochemical study of androgen receptors (ARs), demonstrated for the first time the dipolymers of full-length androgen receptors (ARs) and the three-dimensional structure of the active complex bound to DNA, demonstrated the internal interaction of AR dipolymers and combined with biochemical experiments to reveal the principles of interaction between androgen receptors (ARs) and their associated co-activation factors. It provides a new perspective on possible treatmentoptions for prostate cancer and other related diseases.the paper used frozen electron microscopy technology to conduct structural biology studies of full-length AR dipolymers (ARE-DNA/AR) and active complexes (ARE-DNA/AR/SRC-3/p300), and for the first time demonstrated the complete structure of the two complexes.prior to this study, the researchers had only a local understanding of the three-dimensional structure of androgen receptors (AR), and although the crystal structure of LBD and DBD has been parsed, the previous structural information is still missing ntD portions, which have been thought to be critical to the activity of androgen receptors (AR) by previous biochemical experiments.AR's NTD is relatively conservative in different spinal animals and has a lower similarity to NTD with other nuclear receptors in the family.the study is the first to show the structure of NTD in androgen receptors (AR), finding that this region is the core region in which androgen receptors (ARs) interact with other proteins, and other active co-activators form complexes through NTD interactions with androgen receptors (AR) that regulate gene expression in prostate cancer.researchers found that NTD is at the forefront of androgen receptors (AR), an area where important co-activators such as p300 and SRC-3 bind, and that once co-activated factors combine to form an active complex in NTD, prostate cancer is promoted.this finding is completely different from the binding mechanism of the estrogen receptor (ER alpha) active complex found in the same research group, which is considered a starting factor for breast cancer.although androgen receptors (AR) and estrogen receptors (ER alpha) are the same families of steroid nucleoreceptors and have similar structural compositions, they actually use different active regions to regulate downstream gene expression.previous studies have found that ER alpha is primarily dependent on its C-side region, and this study shows that AR has a strong N-end NTD region as the main active region.affected by estrogen receptor ER alpha, coupled with the lack of NTD part of the structural information, at this stage, the vast majority of nuclear receptor antagonists are developed for the LbD region of the C side, this study shows that this region is not the main functional area of androgen receptor (AR), this paper strongly supports the androgen receptor (AR) NTD target screening for prostate cancer drugs.the study provides a starting point for understanding the role of androgen receptors (AR) as molecular machines in prostate cancer.new findings will provide a whole new way of thinking about the treatment of prostate cancer, creating a broader pharmaceutical landscape. , the study could also help increase understanding of other related diseases and the underlying mechanisms of gene regulation. Dr. Yu Xinzhe, Ph.D., Department of Biochemistry and Molecular Biology, Baylor School of Medicine, and Dr. Yi Ping, Assistant Professor, Department of Molecular and Cell Biology, Baylor School of Medicine, Usain Ince, and Dr. Bert W. O'Malley, Former Dean of the Department of Molecular and Cell Biology at Baylor College of Medicine, usa in the joint report. .