Article
Oncology
Yuichiro Kanno, Nao Saito, Ryota Saito, Tomohiro Kosuge, Ryota Shizu, Tomofumi Yatsu, Takuomi Hosaka, Kiyomitsu Nemoto, Keisuke Kato, Kouichi Yoshinari
Summary: This study investigated the selective mechanism of selective androgen receptor modulators (SARMs) using the synthetic steroid YK11. The results suggested that gene selective regulation by SARMs is achieved through differential DNA-binding and/or cofactor recruitment by ligands. These findings provide novel insights into the mechanism of action of SARMs.
EXPERIMENTAL CELL RESEARCH
(2022)
Article
Medicine, Research & Experimental
Elizabeth L. Kilby, Daniel M. Kelly, T. Hugh Jones
Summary: The study demonstrates that testosterone can promote cholesterol clearance in human macrophages by activating LXRα and downstream targets, potentially explaining the anti-atherogenic effects of testosterone in clinical settings.
Article
Biochemistry & Molecular Biology
Kosuke Yokobori, Masahiko Negishi
Summary: Phosphorylation of androgen receptor at Ser815 plays a crucial role in regulating its functions and biological roles, including stabilizing homodimer formation and influencing ER stress responses.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Godfrey Dzhivhuho, Jordan Holsey, Ethan Honeycutt, Heather O'Farrell, David Rekosh, Marie-Louise Hammarskjold, Patrick E. H. Jackson
Summary: During HIV infection, the transport of viral mRNA from the cell nucleus to the cytoplasm is facilitated by Rev protein and the Rev Response Element (RRE). The activity of Rev protein, which varies among different primary isolates, is determined by amino acid differences within the oligomerization domain. Small sequence changes can modulate Rev-RRE activity, potentially impacting HIV pathogenesis.
SCIENTIFIC REPORTS
(2022)
Article
Oncology
Xiangyou Leng, Mohan Liu, Dachang Tao, Bo Yang, Yangwei Zhang, Tianrong He, Shengyu Xie, Zhaokun Wang, Yunqiang Liu, Yuan Yang
Summary: The study revealed that DNA methylation plays a crucial role in regulating the expression of TSPY1 in prostate cancer, and identified TSPY1 as an androgen-AR axis-regulated oncogene, suggesting a novel and potential target for PCa therapy.
Article
Oncology
Timothy C. Wright, Victoria L. Dunne, Ali H. D. Alshehri, Kelly M. Redmond, Aidan J. Cole, Kevin M. Prise
Summary: In this study, the synergistic effects of AR inhibition with Enzalutamide were found only in AR-sensitive prostate models, while Abiraterone displayed synergistic effects in combination with radiation regardless of AR status, indicating potential alternative mechanisms of action. The underlying mechanisms of AR-based synergy are based on the reduction of key AR-linked DNA repair pathways, leading to increased cell death. Comparison between Abiraterone and Enzalutamide suggested Abiraterone's superiority from a mechanistic standpoint, providing a rationale for selecting Abiraterone over Enzalutamide in combination with radiation therapy.
FRONTIERS IN ONCOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Yuliang Wang, Weijie Gao, Youjia Li, Sin Ting Chow, Wenjuan Xie, Xingxing Zhang, Jianfu Zhou, Franky Leung Chan
Summary: Prostate cancer relies on the androgen receptor-mediated signaling for growth, making hormone or androgen-deprivation therapy a key treatment option. Despite its effectiveness in locally advanced or metastatic cases, most patients will develop resistance, leading to castration-resistant disease or even a more aggressive androgen-independent subtype. These newly identified orphan nuclear receptors (ONRs) have shown potential as biomarkers and therapeutic targets in advanced prostate cancer.
MOLECULAR ASPECTS OF MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Sabine Pinter, Franziska Knodel, Michel Choudalakis, Philipp Schnee, Carolin Kroll, Marina Fuchs, Alexander Broehm, Sara Weirich, Mareike Roth, Stephan A. Eisler, Johannes Zuber, Albert Jeltsch, Philipp Rathert
Summary: In this study, we identified DEAD-box helicase 19A (DDX19A) as a novel coregulator of lysine specific demethylase 1 (LSD1), which regulates gene expression by controlling the trimethylation of lysine 27 on histone 3. This discovery sheds light on a novel transcriptional regulatory pathway involving LSD1, DDX19A, and histone modifications.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Oncology
Kumar Nikhil, Hanan S. Haymour, Mohini Kamra, Kavita Shah
Summary: This study identified that LIMK2 degrades SPOP by direct phosphorylation and creates a feedback loop to promote oncogenicity in prostate cancer. Understanding the relationship between LIMK2 and SPOP provides a powerful opportunity to inhibit LIMK2 and retain WT-SPOP, effectively halting disease progression.
BRITISH JOURNAL OF CANCER
(2021)
Article
Biochemistry & Molecular Biology
Kyong-Oh Shin, Sungeun Kim, Byeong Deog Park, Yoshikazu Uchida, Kyungho Park
Summary: Studies have shown that the analog of endocannabinoid, PS, can stimulate the generation of ceramides in inflamed skin cells. This increase in specific ceramide species as well as total ceramide content is mediated by the endocannabinoid receptor CB1, enhancing the function of the epidermal permeability barrier.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell Biology
Katie Joanna Miller, Mohammad Asim
Summary: The androgen receptor (AR) signalling pathway plays a key role in prostate cancer. Upstream kinases promote AR signalling, while other kinases are regulated by AR. These kinases represent potential therapeutic targets for PCa.
Article
Biochemistry & Molecular Biology
Jacobus C. Buurstede, Susana N. Paul, Karolien De Bosscher, Onno C. Meijer, Jan Kroon
Summary: Glucocorticoids exert their effects by activating the glucocorticoid receptor (GR) throughout the body. This study investigated the interaction between glucocorticoids and androgen signaling in the liver transcriptome. The results showed that a substantial proportion of the hepatic transcriptome is androgen-dependent after chronic exposure, while the effects of glucocorticoids are largely androgen-independent after acute exposure. The study suggests that prolonged glucocorticoid exposure may upregulate androgen receptor expression, leading to androgen dependence not driven by direct interactions between the androgen receptor and glucocorticoid receptor.
Article
Biochemistry & Molecular Biology
Dhirodatta Senapati, Vikas Sharma, Santosh Kumar Rath, Uddipak Rai, Naresh Panigrahi
Summary: The article discusses the role of the androgen receptor in prostate cancer and the mechanisms of resistance. It highlights the plasticity of AR-DNA binding and emphasizes the importance of developing alternative strategies to antagonize AR activity.
Article
Oncology
Jing Wei, Lijuan Yin, Jingjing Li, Jing Wang, Tianjie Pu, Peng Duan, Tzu-Ping Lin, Allen C. Gao, Boyang Jason Wu
Summary: The study reveals a reciprocal regulatory circuit between MAOA and AR in prostate cancer, with implications for cancer development and growth, particularly CRPC. Targeting MAOA may enhance the efficacy of AR-targeted therapies.
Review
Biochemistry & Molecular Biology
Emma J. Montgomery, Enming Xing, Moray J. Campbell, Pui-Kai Li, James S. Blachly, Allan Tsung, Christopher C. Coss
Summary: Hepatocellular carcinoma (HCC) is a common type of liver cancer and a leading cause of cancer-related death worldwide. The androgen receptor (AR) has been found to play an important role in HCC, although current AR-targeted therapies have not shown efficacy in HCC. However, by building upon research in prostate cancer (PCa), potential AR-targeted therapeutic approaches for HCC could be developed.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Natalia Dworak, Dawid Makosa, Mandovi Chatterjee, Kasey Jividen, Chun-Song Yang, Chelsi Snow, William C. Simke, Isaac G. Johnson, Joshua B. Kelley, Bryce M. Paschal
Article
Biochemical Research Methods
Joshua B. Kelley, Bryce M. Paschal
Article
Multidisciplinary Sciences
Travis J. Loya, Thomas W. O'Rourke, William C. Simke, Joshua B. Kelley, Daniel Reines
Article
Cell Biology
Erin C. Bailey, Sarah S. Alrowaished, Elisabeth A. Kilroy, Emma S. Crooks, Daisy M. Drinkert, Chaya M. Karunasiri, Joseph J. Belanger, Andre Khalil, Joshua B. Kelley, Clarissa A. Henry
Article
Biochemistry & Molecular Biology
Nambirajan Rangarajan, Claire L. Gordy, Lauren Askew, Samantha M. Bevill, Timothy C. Elston, Beverly Errede, Jillian H. Hurst, Joshua B. Kelley, Joshua B. Sheetz, Sara Kimiko Suzuki, Natalie H. Valentin, Everett Young, Henrik G. Dohlman
JOURNAL OF BIOLOGICAL CHEMISTRY
(2019)
Article
Microbiology
Allison K. Scherer, Bailey A. Blair, Jieun Park, Brittany G. Seman, Joshua B. Kelley, Robert T. Wheeler
Article
Cell Biology
Teddy Kamata, Chun-Song Yang, Tiffany A. Melhuish, Henry F. Frierson Jr., David Wotton, Bryce M. Paschal
Summary: PARP7, a member of the PARP family, is involved in ADP-ribosylation and potentially acts as a tumor suppressor in breast, ovarian, and colorectal cancer. In prostate cancer cells, PARP7 is regulated by androgen signaling both at the transcriptional and post-transcriptional levels, with its protein structure finely tuned for rapid turnover.
Article
Biochemistry & Molecular Biology
Holly V. Goodson, Joshua B. Kelley, Susan H. Brawley
Summary: The cytoskeleton plays a central role in eukaryotic biology, and although red algae surprisingly lack key cytoskeletal elements based on recent genomic analysis, testable models have been proposed to explain how red algal cells may perform various processes. This research not only enhances understanding of red algae and related lineages, but also sheds light on cytoskeletal processes in animal cells.
Article
Multidisciplinary Sciences
Chun-Song Yang, Kasey Jividen, Teddy Kamata, Natalia Dworak, Luke Oostdyk, Bartlomiej Remlein, Yasin Pourfarjam, In-Kwon Kim, Kang-Ping Du, Tarek Abbas, Nicholas E. Sherman, David Wotton, Bryce M. Paschal
Summary: Androgen receptor (AR) signaling is regulated by multiple post-translational modifications. The authors identify the writer and reader enzymes for AR ADP-ribosylation and show how they modulate AR signaling output in prostate cancer cells.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Teddy Kamata, Chun-Song Yang, Bryce M. Paschal
Summary: The research uncovers the regulation of androgen receptor by PARP7 through ADP-ribosylation, which requires nuclear localization and agonist-induced conformation. The zinc finger structure of PARP7 plays a crucial role in modulating AR ADP-ribosylation, with effects separable from nuclear import.
BIOCHEMICAL JOURNAL
(2021)
Article
Biochemistry & Molecular Biology
Yashwanth Ashok, Carlos Vela-Rodriguez, Chunsong Yang, Heli I. Alanen, Fan Liu, Bryce M. Paschal, Lari Lehtio
Summary: This study provides insights into the mechanism of ADP-ribosylation and ubiquitination mediated by DTX3L-PARP9 through intra- and inter-subunit interactions.
BIOCHEMICAL JOURNAL
(2022)
Article
Endocrinology & Metabolism
Karolina Sienkiewicz, Chunsong Yang, Bryce M. Paschal, Aakrosh Ratan
Summary: This study conducted whole-genome sequencing and analysis of LNCaP, VCaP, and PC3 cell lines, revealing the presence of multiple subpopulations in LNCaP cells leading to nonintegral copy number states and a high mutational load; all three cell lines harbored mutations in genes involved in DNA repair and other critical cellular processes; PC3-AR cells had a truncating mutation in TP53, while VCaP cells contained a gain-of-function mutation promoting cancer invasion and metastasis.
Article
Genetics & Heredity
Jeremy C. Hunn, Katherine M. Hutchinson, Joshua B. Kelley, Daniel Reines
Summary: Reorganization of cellular proteins into subcellular compartments is a well-recognized physiological process. In yeast cells, the rearrangement of the Nab3 transcription termination factor plays a crucial role in protein condensation and granule formation. However, the mechanisms of subnuclear compartment formation are still not well understood.
Article
Oncology
Chunsong Yang, Krzysztof Wierbilowicz, Natalia M. Dworak, Song Yi Bae, Sachi B. Tengse, Nicki Abianeh, Justin M. Drake, Tarek Abbas, Aakrosh Ratan, David Wotton, Bryce M. Paschal
Summary: The ADP-ribosyltransferase PARP7 affects gene expression and protein function in prostate cancer cells by conjugating ADP-ribose to acceptor amino acids. A recently developed inhibitor, RBN2397, inhibits androgen-induced ADP-ribosylation in prostate cancer cells and reduces cell growth. RBN2397 also affects PARP7 localization and may be an actionable target in advanced prostate cancer.
CANCER RESEARCH COMMUNICATIONS
(2023)