Article
Medicine, Research & Experimental
Sue Jin Moon, Byong Chang Jeong, Hwa Jin Kim, Joung Eun Lim, Hye-Jeong Kim, Ghee Young Kwon, Joshua A. Jackman, Jeong Hoon Kim
Summary: The study identified BCT as a potent inhibitor targeting both AR-FL and AR-V7 activities in CRPC, effectively suppressing tumor growth and metastasis. Mechanistically, BCT disrupts the interaction of HSP90 with AR-FL/AR-V7, leading to their degradation and showing promising therapeutic potential against CRPC.
Review
Biochemistry & Molecular Biology
Mu Lv, Juanjuan Yu, Yan Huang, Jie Ma, Jun Xiang, Yanqiu Wang, Linxia Li, Zhenbo Zhang, Hong Liao
Summary: Uterine diseases, such as endometriosis and uterine fibroids, have a significant impact on women's health. Androgens, primarily synthesized in the ovaries and adrenal glands, play a crucial role in the development of these diseases. However, further research is needed to understand the signaling pathways involved and develop targeted therapeutic strategies.
Article
Endocrinology & Metabolism
Oscar Horwath, Marcus Moberg, Angelica Linden Hirschberg, Bjorn Ekblom, William Apro
Summary: Moderate-dose testosterone administration has no effect on molecular regulators of muscle protein turnover and mitochondrial remodeling in young women.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Waqas Azeem, Jan Roger Olsen, Margrete Reime Hellem, Yaping Hua, Kristo Marvyin, Xisong Ke, Anne Margrete oyan, Karl-Henning Kalland
Summary: This study investigated the role of GATA2 in prostate epithelial cells and found that exogenous GATA2 protein was rapidly degraded and its expression could be rescued by proteasome inhibitors. The inhibition of proteasome also induced the transcription of AR mRNA and luminal marker genes in prostate cells. Different intrinsic mechanisms restricted the expression of GATA2 in these cells. These findings suggest the existence of crucial cofactors for AR mRNA expression and luminal differentiation at the proteolytic level.
Article
Infectious Diseases
Ashfaq Ahmad, Zhandaulet Makhmutova, Wenwen Cao, Sidra Majaz, Amr Amin, Yingqiu Xie
Summary: By using AlphaFold multimer, network and single cells database analyses, the study revealed the specificity of Androgen receptor (AR) against spike receptor binding protein (RBD) of SARS-CoV-2. AR preferred to bind the LYRL motif and showed reduced affinity against Omicron. Network analysis indicated the involvement of AR-related genes in T-cell signaling regulation and spatial location of CD8+ T-cells in AR+ single cells. These findings provide insights into the interaction between AR and immune response, and suggest AR as a potential therapeutic target for anti-Omicron new lineages.
EXPERT REVIEW OF ANTI-INFECTIVE THERAPY
(2023)
Article
Pharmacology & Pharmacy
Kenneth A. Jacobson, Adriaan P. IJzerman, Christa E. Mueller
Summary: This review paper explores the historical origins of P2 receptors and adenosine receptor ligands, emphasizing the versatility of common chemical scaffolds for multiple receptor targets. By analyzing structure activity relationships, selective receptor subtype targeting can be achieved, leading to potential therapeutic applications in various diseases.
BIOCHEMICAL PHARMACOLOGY
(2021)
Article
Oncology
Louis Lacombe, Helene Hovington, Herve Brisson, Sadia Mehdi, Deborah Beilevaire, Jean-Philippe Emond, Antoine Wagner, Lyne Villeneuve, David Simonyan, Veronique Ouellet, Veronique Barres, Mathieu Latour, Armen Aprikian, Alain Bergeron, Vincent Castonguay, Felix Couture, Simone Chevalier, Fadi Brimo, Ladan Fazli, Neil Fleshner, Martin Gleave, Pierre I. Karakiewicz, Jean-Baptiste Lattouf, Dominique Trudel, Theodorus Van der Kwast, Anne-Marie Mes-Masson, Frederic Pouliot, Yves Fradet, Etienne Audet-Walsh, Fred Saad, Chantal Guillemette, Eric Levesque
Summary: UGT2B28, a pathway involved in androgen inactivation, has been identified as a predictor of progression in localized prostate cancer. This study demonstrated that UGT2B28 is overexpressed in tumors and associated with inferior clinical outcomes. Functional analysis revealed that UGT2B28 promotes cell proliferation and its expression is regulated by the androgen receptor (AR)/ARv7. Furthermore, UGT2B28 interacts with huntingtin-interacting protein 1 (HIP1) to activate AR/epidermal growth factor receptor (EGFR) pathways, leading to cell proliferation and epithelial-to-mesenchymal transition (EMT).
Article
Multidisciplinary Sciences
Mark D. Long, Vineet K. Dhiman, Hayley C. Affronti, Qiang Hu, Song Liu, Dominic J. Smiraglia
Summary: Understanding the epigenetic control of normal differentiation programs can provide valuable information about the disrupted regulatory states in cancer. By studying the luminal cell differentiation trajectory in prostate cancer cells exposed to androgens, and analyzing DNA methylation dynamics using whole genome bisulfite sequencing, researchers found that aberrant methylation patterns observed in prostate cancer are influenced by the normal dynamics of DNA methylation in the luminal differentiation program.
SCIENTIFIC REPORTS
(2021)
Review
Biochemistry & Molecular Biology
Tae Jin Kim, Young Hwa Lee, Kyo Chul Koo
Summary: The androgen receptor (AR) plays a crucial role in the development and progression of prostate cancer (PCa), and treatment for hormone-sensitive prostate cancer (HSPC) relies heavily on androgen deprivation therapy (ADT). Despite most patients progressing to castration-resistant prostate cancer (CRPC), studies suggest that manipulating alternative molecular pathways can help improve current treatments and develop novel therapies for CRPC management.
Article
Chemistry, Multidisciplinary
Shiting Zhao, Tao Nie, Lei Li, Qiaoyun Long, Ping Gu, Yuwei Zhang, Wei Sun, Zexin Lin, Qing Liu, Yue Qi, Wei Wang, Mengyuan Xie, Kerry Loomes, Chenleng Cai, Donghai Wu, Hannah Xiaoyan Hui
Summary: PRDM16 is a dominant activator of brown and beige adipocytes. The regulation of PRDM16 expression is not fully understood. Androgen receptor (AR) is negatively correlated with PRDM16 expression. Sex differences in PRDM16 mRNA expression are observed in human WAT, with females having higher expression than males. Androgen-AR signaling inhibits PRDM16 expression and beige adipocyte browning. AR directly binds to the intronic region of PRDM16, but not to Ucp1 and other browning-related genes. Adipocyte-specific deletion of Ar promotes beige cell biogenesis, while adipocyte-specific overexpression of AR attenuates white adipose beiging.
Review
Biotechnology & Applied Microbiology
Stefania Stella, Federica Martorana, Michele Massimino, Silvia Rita Vitale, Livia Manzella, Paolo Vigneri
Summary: Luminal Androgen Receptor Breast Cancers (LAR BCs) are a subtype of triple negative breast cancer with unique characteristics, accounting for about 10% of cases. The complexity of androgen receptor activity in LAR BCs offers therapeutic opportunities beyond AR inhibition, such as targeting PI3K/mToR, HER2, BRCA1, cell cycle, and immune modulation pathways. While anti-androgen therapies have been tested in clinical trials, the results have been inconsistent. Studies exploring combinations of anti-androgen agents with other targeted therapies are currently ongoing. Efforts should focus on finding biological vulnerabilities in LAR BCs to identify new and effective therapeutic targets.
ONCOTARGETS AND THERAPY
(2023)
Article
Medicine, Research & Experimental
Anna Pluciennik, Yuhong Liu, Elana Molotsky, Gregory B. Marsh, Bedri Ranxhi, Frederick J. Arnold, Sophie St.-Cyr, Beverly Davidson, Naemeh Pourshafie, Andrew P. Lieberman, Wei Gu, Sokol V. Todi, Diane E. Merry
Summary: This study identified the critical role of USP7 in the pathophysiology of spinal and bulbar muscular atrophy (SBMA), showing that reducing USP7 levels can decrease mutant AR aggregation and toxicity. The findings also suggest a similar role for USP7 in other diseases such as spinocerebellar ataxia type 3 (SCA3) and Huntington's disease.
JOURNAL OF CLINICAL INVESTIGATION
(2021)
Review
Pharmacology & Pharmacy
Agata Kodron, Ben Hur Mussulini, Iwona Pilecka, Agnieszka Chacinska
Summary: Proteasome dysfunction can lead to protein toxicity and mitochondrial dysfunction, while mitochondrial impairment can cause protein oxidation and misfolding leading to proteasome overload.
PHARMACOLOGICAL RESEARCH
(2021)
Article
Immunology
Yan Fang, Pengcheng Sun, Xuping Xie, Mingjian Du, Fenghe Du, Jianfeng Ye, Birte K. Kalveram, Jessica A. Plante, Kenneth S. Plante, Bo Li, Xiao-chen Bai, Pei-Yong Shi, Zhijian J. Chen
Summary: The study utilized LIBRA-seq technology to identify an antibody, SW186, that exhibits broad neutralizing activity against various SARS-CoV-2 variants. The cryo-EM structure analysis revealed that SW186 targets a conserved epitope on the receptor binding domain of the viral spike protein. In mouse models, administration of SW186 significantly reduced viral loads in the lungs.
SCIENCE IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Zsuzsanna Rethi-Nagy, Edit Abraham, Katalin Udvardy, Eva Klement, Zsuzsanna Darula, Margit Pal, Robert L. Katona, Vilmos Tubak, Tibor Pali, Zoltan Kota, Rita Sinka, Andor Udvardy, Zoltan Lipinszki
Summary: In this study, we identified and characterized a 13-mer protein segment derived from the p54/Rpn10 ubiquitin receptor subunit of the Drosophila 26S proteasome, named STABILON. Attachment of STABILON to unstable proteins significantly increased their concentration, and STABILON also acted as a dual function motif by increasing the concentration of corresponding mRNAs and preventing degradation of short-lived fusion proteins.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)