Article
Oncology
Corinna Kosnopfel, Simone Wendlinger, Heike Niessner, Johannes Siewert, Tobias Sinnberg, Angelika Hofmann, Jonas Wohlfarth, David Schrama, Marion Berthold, Claudia Siedel, Birgit Sauer, Aarthi Jayanthan, Georg Lenz, Sandra E. Dunn, Bastian Schilling, Birgit Schittek
Summary: Inhibition of p90 ribosomal S6 kinases (RSK) has demonstrated anti-tumor effects in malignant melanoma with hyperactivated MAPK signaling, regardless of the genetic subgroups. RSK inhibition not only suppresses tumor cell growth and survival, but also promotes tumor cell differentiation and immunogenicity, leading to enhanced T-cell activation and melanoma cell killing.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2023)
Review
Cardiac & Cardiovascular Systems
Muna Suleiman, Afnan Al Najjar, Zain Z. Zakaria, Rashid Ahmed, Huseyin C. Yalcin, Hesham M. Korashy, Shahab Uddin, Sadaf Riaz, Nabeel Abdulrahman, Fatima Mraiche
Summary: Targeted therapy, such as TKIs, has been approved for managing cancer, but TKI-induced cardiotoxicity limits their use. Investigating potential cardioprotective techniques to combine with TKIs has become necessary.
JOURNAL OF CARDIOVASCULAR TRANSLATIONAL RESEARCH
(2023)
Review
Pharmacology & Pharmacy
Fani Koutsougianni, Dimitra Alexopoulou, Ayca Uvez, Andromachi Lamprianidou, Evangelia Sereti, Chrisiida Tsimplouli, Elif Ilkay Armutak, Konstantinos Dimas
Summary: The 90 kDa ribosomal S6 kinase (RSK) family of proteins, downstream effectors of the Ras/ERK/MAPK signaling cascade, play important roles in various cellular processes and have been implicated in cancer. This review summarizes recent advances in RSK signaling, including biological insights, functions, mechanisms associated with carcinogenesis, and the development of pharmacological inhibitors for potential anticancer therapeutic strategies.
BIOCHEMICAL PHARMACOLOGY
(2023)
Review
Endocrinology & Metabolism
Deborah A. Lannigan
Summary: This review focuses on the coordination between ERK1/2-RSK2 and estrogen signaling through ERα, and their interrelationships at the levels of transcription, translation, and posttranslational modification. Understanding how they cooperate in homeostasis and disease may lead to new therapeutic approaches for estrogen-dependent disorders.
Article
Microbiology
Zhenshan Liu, Chengrong Liu, Xin Wang, Wenwei Li, Jingfan Zhou, Peixian Dong, Maggie Z. X. Xiao, Chunxia Wang, Yucai Zhang, Joyce Fu, Fanxiu Zhu, Qiming Liang
Summary: RSK1 is SUMOylated at lysine residues K110, K335, and K421 during KSHV lytic replication, which is essential for efficient viral replication. The SUMOylation of RSK1 regulates the phosphorylation of downstream substrates, such as eIF4B, and is crucial for KSHV lytic replication.
Article
Virology
Ning Han, Qingbo Zhang, Xiaoqiong Tang, Lang Bai, Libo Yan, Hong Tang
Summary: Hepatitis B virus (HBV) infection is a major cause of hepatocellular carcinoma (HCC), and the Hepatitis B virus X-protein (HBx) has been found to upregulate the expression of RSK2, promoting the proliferation of HCC cells. RSK2 and CREB may serve as potential prognostic markers for HCC patients.
Article
Biochemistry & Molecular Biology
Ae-Rang Hwang, Hee-Jung Lee, Suji Kim, Seong-Hee Park, Chang-Hoon Woo
Summary: Inhibition of phosphorylated p90RSK with specific inhibitors, such as FMK or BI-D1870, can suppress PDGF-BB-induced migration and proliferation of vascular smooth muscle cells (VSMCs), reduce phenotypic changes and extracellular matrix accumulation in VSMCs. It can also affect VSMC proliferation by regulating the expression of cyclin D1 and cyclin-dependent kinase-4, and inhibit the decrease of Cdk inhibitor p27 expression induced by PDGF-BB, thereby inhibiting VSMC proliferation in the G0/G1 phase. The use of phosphorylated p90RSK inhibitors can attenuate the PDGF-BB-induced phenotypic switch and neointimal hyperplasia in VSMCs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Anita Alexa, Peter Sok, Fridolin Gross, Krisztian Albert, Evan Kobori, Adam L. Poti, Gergo Gogl, Isabel Bento, Ersheng Kuang, Susan S. Taylor, Fanxiu Zhu, Andrea Ciliberto, Attila Remenyi
Summary: The herpesvirus protein ORF45 can bind to host kinases ERK and RSK, affecting cell signaling by interfering with the host kinases' docking systems. It uses optimized linear binding motifs to hijack the ERK-RSK complex and manipulate ERK-RSK signaling, resulting in enhanced kinase protection and selective up-regulation of RSK substrate phosphorylation.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Eleonore W. E. Verweij, Reggie Bosma, Meichun Gao, Jelle van den Bor, Betty Al Araaj, Sabrina M. de Munnik, Xiaoyuan Ma, Rob Leurs, Henry F. Vischer
Summary: This study used bioluminescence resonance energy transfer (BRET)-based biosensors to measure the effects of different agonists on the H1R signaling pathway, and found that one of the agonists exhibited biased agonism.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Eric B. Wright, Shinji Fukuda, Mingzong Li, Yu Li, George A. O'Doherty, Deborah A. Lannigan
Summary: The study identified a natural product, SL0101, that binds specifically to RSK1/2 by inducing conformational rearrangement, but not to RSK3/4 due to a single amino acid difference. Kinetic analysis revealed that regions outside of the N-terminal kinase domain also contribute to stable inhibitor binding towards RSK2. Additionally, a modification on SL0101 was discovered to form a highly stable inhibitor complex with RSK2, suggesting potential for identifying RSK2-specific inhibitors.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2021)
Review
Pathology
Junpeng Xu, Qingge Jia, Yan Zhang, Yuan Yuan, Tianqi Xu, Kangjie Yu, Jia Chai, Kaijing Wang, Ligang Chen, Tian Xiao, Mingyang Li
Summary: RSK4 is a Ser/Thr protein kinase that regulates cell survival and proliferation in various types of cancer. Its role as a tumor suppressor gene or an oncogene is controversial, and specific inhibitors for RSK4 have not been found.
PATHOLOGY RESEARCH AND PRACTICE
(2021)
Article
Medicine, Research & Experimental
Masaki Arioka, Fumi Seto-Tetsuo, Takeru Inoue, Koichi Miura, Shin Ishikane, Kazunobu Igawa, Katsuhiko Tomooka, Fumi Takahashi-Yanaga, Toshiyuki Sasaguri
Summary: This study reveals that DIF-1 reduces the adhesion of tumor cells to blood vessels by inhibiting mTORC1-S6K signaling and decreasing the expression of adhesion molecule VCAM-1 on vascular endothelial cells. These findings highlight the potential of DIF-1 as a promising compound for the development of anti-cancer drugs with anti-metastatic properties.
Article
Cell Biology
Stelios Chrysostomou, Rajat Roy, Filippo Prischi, Lucksamon Thamlikitkul, Kathryn L. Chapman, Uwais Mufti, Robert Peach, Laifeng Ding, David Hancock, Christopher Moore, Miriam Molina-Arcas, Francesco Mauri, David J. Pinato, Joel M. Abrahams, Silvia Ottaviani, Leandro Castellano, Georgios Giamas, Jennifer Pascoe, Devmini Moonamale, Sarah Pirrie, Claire Gaunt, Lucinda Billingham, Neil M. Steven, Michael Cullen, David Hrouda, Mathias Winkler, John Post, Philip Cohen, Seth J. Salpeter, Vered Bar, Adi Zundelevich, Shay Golan, Dan Leibovici, Romain Lara, David R. Klug, Sophia N. Yaliraki, Mauricio Barahona, Yulan Wang, Julian Downward, J. Mark Skehel, Maruf M. U. Ali, Michael J. Seckl, Olivier E. Pardo
Summary: The study identified RSK4 as a driver of drug resistance and metastasis in lung and bladder cancer cells, and silencing this kinase increased sensitivity to chemotherapy and reduced metastasis. Drug screening revealed fluoroquinolone antibiotics as potent RSK4 inhibitors, with trovafloxacin replicating effects of RSK4 silencing. Further structural analysis provided insights into how trovafloxacin blocks RSK4 kinase activation. Additionally, patients receiving chemotherapy and prophylactic levofloxacin showed significantly prolonged overall survival, suggesting RSK4 inhibition as a potential therapeutic strategy for lung and bladder cancer.
SCIENCE TRANSLATIONAL MEDICINE
(2021)
Article
Neurosciences
Yaping Chu, Jeffrey H. Kordower
Summary: The study suggests that the lack of efficacy of glial cell derived neurotropic factor in Parkinson's disease patients may be attributed to alterations in signaling receptors and downstream signaling molecules. This is supported by findings showing reductions in RET and phosphorylated ribosomal protein S6 levels in patients with minimal motor deficits or Parkinson's disease.
NEUROBIOLOGY OF DISEASE
(2021)
Article
Biochemistry & Molecular Biology
Fabian Arechavaleta-Velasco, Pablo Dominguez-Lopez, Ernesto Acosta-Jimenez, Laura Diaz-Cueto
Summary: RSK4 promoter methylation is increased in malignant ovarian tumors, but this does not regulate its expression in ovarian cancer. Reactivation of RSK4 only reduces cell proliferation in the endometrioid histological subtype.
MOLECULAR BIOLOGY REPORTS
(2023)
Article
Chemistry, Medicinal
Michael L. Martini, Jing Liu, Caroline Ray, Xufen Yu, Xi-Ping Huang, Aarti Urs, Nikhil Urs, John D. McCorvy, Marc G. Caron, Bryan L. Roth, Jian Jin
JOURNAL OF MEDICINAL CHEMISTRY
(2019)
Article
Multidisciplinary Sciences
Reed M. Stein, Hye Jin Kang, John D. McCorvy, Grant C. Glatfelter, Anthony J. Jones, Tao Che, Samuel Slocum, Xi-Ping Huang, Olena Savych, Yurii S. Moroz, Benjamin Stauch, Linda C. Johansson, Vadim Cherezov, Terry Kenakin, John J. Irwin, Brian K. Shoichet, Bryan L. Roth, Margarita L. Dubocovich
Editorial Material
Multidisciplinary Sciences
Brian Krumm, Bryan L. Roth
Editorial Material
Biochemistry & Molecular Biology
Brian Krumm, Bryan L. Roth
Article
Multidisciplinary Sciences
Tao Che, Justin English, Brian E. Krumm, Kuglae Kim, Els Pardon, Reid H. J. Olsen, Sheng Wang, Shicheng Zhang, Jeffrey F. Diberto, Noah Sciaky, F. Ivy Carroll, Jan Steyaert, Daniel Wacker, Bryan L. Roth
NATURE COMMUNICATIONS
(2020)
Article
Biology
Nilkanth Patel, Xi Ping Huang, Jessica M. Grandner, Linda C. Johansson, Benjamin Stauch, John D. McCorvy, Yongfeng Liu, Bryan Roth, Vsevolod Katritch
Article
Biochemical Research Methods
May Fern Toh, Julie M. Brooks, Tim Strassmaier, Rodolfo J. Haedo, Corey B. Puryear, Bruce L. Roth, Kosalvisal Ouk, Sokhom S. Pin
Meeting Abstract
Biochemistry & Molecular Biology
Abdelfattah Faouzi, Saheem Zaidi, Tao Che, Chad Kormos, Tiffany Zhang, Manish Madasu, Shainnel Eans, Chloe Simons, Ying-Xian Pan, Jay McLaughlin, Ivy Carroll, Ream Al Hassani, Bryan Roth, Vsevolod Katritch, Susruta Majumdar
Meeting Abstract
Biochemistry & Molecular Biology
Grant Glatfelter, Reed Stein, Hye Kang, Anthony Jones, John Irwin, Bryan Roth, Brian Shoichet, Margarita Dubocovich
Article
Multidisciplinary Sciences
David E. Gordon, Gwendolyn M. Jang, Mehdi Bouhaddou, Jiewei Xu, Kirsten Obernier, Kris M. White, Matthew J. O'Meara, Veronica V. Rezelj, Jeffrey Z. Guo, Danielle L. Swaney, Tia A. Tummino, Ruth Huttenhain, Robyn M. Kaake, Alicia L. Richards, Beril Tutuncuoglu, Helene Foussard, Jyoti Batra, Kelsey Haas, Maya Modak, Minkyu Kim, Paige Haas, Benjamin J. Polacco, Hannes Braberg, Jacqueline M. Fabius, Manon Eckhardt, Margaret Soucheray, Melanie J. Bennett, Merve Cakir, Michael J. McGregor, Qiongyu Li, Bjoern Meyer, Ferdinand Roesch, Thomas Vallet, Alice Mac Kain, Lisa Miorin, Elena Moreno, Zun Zar Chi Naing, Yuan Zhou, Shiming Peng, Ying Shi, Ziyang Zhang, Wenqi Shen, Ilsa T. Kirby, James E. Melnyk, John S. Chorba, Kevin Lou, Shizhong A. Dai, Inigo Barrio-Hernandez, Danish Memon, Claudia Hernandez-Armenta, Jiankun Lyu, Christopher J. P. Mathy, Tina Perica, Kala Bharath Pilla, Sai J. Ganesan, Daniel J. Saltzberg, Ramachandran Rakesh, Xi Liu, Sara B. Rosenthal, Lorenzo Calviello, Srivats Venkataramanan, Jose Liboy-Lugo, Yizhu Lin, Xi-Ping Huang, YongFeng Liu, Stephanie A. Wankowicz, Markus Bohn, Maliheh Safari, Fatima S. Ugur, Cassandra Koh, Nastaran Sadat Savar, Quang Dinh Tran, Djoshkun Shengjuler, Sabrina J. Fletcher, Michael C. O'Neal, Yiming Cai, Jason C. J. Chang, David J. Broadhurst, Saker Klippsten, Phillip P. Sharp, Nicole A. Wenzell, Duygu Kuzuoglu-Ozturk, Hao-Yuan Wang, Raphael Trenker, Janet M. Young, Devin A. Cavero, Joseph Hiatt, Theodore L. Roth, Ujjwal Rathore, Advait Subramanian, Julia Noack, Mathieu Hubert, Robert M. Stroud, Alan D. Frankel, Oren S. Rosenberg, Kliment A. Verba, David A. Agard, Melanie Ott, Michael Emerman, Natalia Jura, Mark von Zastrow, Eric Verdin, Alan Ashworth, Olivier Schwartz, Christophe D'Enfert, Shaeri Mukherjee, Matt Jacobson, Harmit S. Malik, Danica G. Fujimori, Trey Ideker, Charles S. Craik, Stephen N. Floor, James S. Fraser, John D. Gross, Andrej Sali, Bryan L. Roth, Davide Ruggero, Jack Taunton, Tanja Kortemme, Pedro Beltrao, Marco Vignuzzi, Adolfo Garcia-Sastre, Kevan M. Shokat, Brian K. Shoichet, Nevan J. Krogan
Article
Biochemistry & Molecular Biology
Reid H. J. Olsen, Jeffrey F. DiBerto, Justin G. English, Alexis M. Glaudin, Brian E. Krumm, Samuel T. Slocum, Tao Che, Ariana C. Gavin, John D. McCorvy, Bryan L. Roth, Ryan T. Strachan
NATURE CHEMICAL BIOLOGY
(2020)
Article
Neurosciences
Yuji Nagai, Naohisa Miyakawa, Hiroyuki Takuwa, Yukiko Hori, Kei Oyama, Bin Ji, Manami Takahashi, Xi-Ping Huang, Samuel T. Slocum, Jeffrey F. DiBerto, Yan Xiong, Takuya Urushihata, Toshiyuki Hirabayashi, Atsushi Fujimoto, Koki Mimura, Justin G. English, Jing Liu, Ken-ichi Inoue, Katsushi Kumata, Chie Seki, Maiko Ono, Masafumi Shimojo, Ming-Rong Zhang, Yutaka Tomita, Jin Nakahara, Tetsuya Suhara, Masahiko Takada, Makoto Higuchi, Jian Jin, Bryan L. Roth, Takafumi Minamimoto
NATURE NEUROSCIENCE
(2020)
Article
Biochemistry & Molecular Biology
Xi-Ping Huang, Terrence P. Kenakin, Shuo Gu, Brian K. Shoichet, Bryan L. Roth
Article
Biochemistry & Molecular Biology
Kuglae Kim, Tao Che, Ouliana Panova, Jeffrey F. DiBerto, Jiankun Lyu, Brian E. Krumm, Daniel Wacker, Michael J. Robertson, Alpay B. Seven, David E. Nichols, Brian K. Shoichet, Georgios Skiniotis, Bryan L. Roth
Article
Multidisciplinary Sciences
Joshua Pottel, Duncan Armstrong, Ling Zou, Alexander Fekete, Xi-Ping Huang, Hayarpi Torosyan, Dallas Bednarczyk, Steven Whitebread, Barun Bhhatarai, Guiqing Liang, Hong Jin, S. Nassir Ghaemi, Samuel Slocum, Katalin V. Lukacs, John J. Irwin, Ellen L. Berg, Kathleen M. Giacomini, Bryan L. Roth, Brian K. Shoichet, Laszlo Urban