Article
Biochemistry & Molecular Biology
Litong Yao, Qian Hao, Mozhi Wang, Yuhai Chen, Hongyi Cao, Qiang Zhang, Keda Yu, Yizhou Jiang, Zhiming Shao, Xiang Zhou, Yingying Xu
Summary: In this study, researchers identified KLHL29 as a crucial tumor suppressor that regulates chemosensitivity in triple-negative breast cancer (TNBC). Low levels of KLHL29 were associated with unfavorable prognoses. Mechanistically, KLHL29 suppressed TNBC growth by degrading DDX3X and inhibiting cell cycle progression. The combination of DDX3X inhibitor RK33 and platinum-based chemotherapy showed promising results in suppressing TNBC.
Article
Oncology
Hyeongjwa Choi, Juntae Kwon, Min Soon Cho, Yifan Sun, Xiaofeng Zheng, Jing Wang, Kerrie B. Bouker, John L. Casey, Michael B. Atkins, Jeffrey Toretsky, Cecil Han
Summary: Depletion of DDX3X triggers a tumor-intrinsic type I IFN response in breast cancer cells, enhancing antitumor activity. Interaction between DDX3X and dsRNA-editing ADAR1 synergistically activates the dsRNA pathway in breast cancer cells.
Article
Oncology
Jie Zhou, Zengjie Lei, Jianfang Chen, Shengbo Liao, Yanrong Chen, Chengxiang Liu, Shuo Huang, Liuli Li, Yan Zhang, Pei Wang, Yinghui Huang, Jianjun Li, Houjie Liang
Summary: The study found that BATF2 is mainly localized in the cytoplasm rather than the nucleus of colorectal cancer (CRC) cells, and that cytoplasmic BATF2 expression is inversely correlated with CRC patient prognosis. The nuclear export and ubiquitin-mediated degradation of BATF2 in CRC cells were identified, revealing a functional nuclear export sequence (NES) in BATF2 through which it binds to CRM1 and translocates out of the nucleus, ultimately enhancing CRC growth via the AP-1/cyclin D1/pRb signaling pathway. Inhibiting nuclear export of BATF2 by mutating its NES or inhibiting CRM1 expression may be a promising therapeutic strategy for CRC.
CLINICAL AND TRANSLATIONAL MEDICINE
(2023)
Review
Oncology
Katherine L. B. Borden
Summary: This review highlights the importance of RNA export in cellular trafficking and the aberrant phenomena observed in cancer. Studies on RNA export machinery and relevant NPC components offer potential therapeutic strategies for targeting cancer.
Article
Biochemistry & Molecular Biology
Sarah Venus, Kaba Tandjigora, Eckhard Jankowsky
Summary: The protein K7 from vaccinia virus is shown to inhibit the biochemical activities and cellular functions of DDX3X by binding to its N-terminus, restraining its association with stress granules.
JOURNAL OF MOLECULAR BIOLOGY
(2023)
Review
Pharmacology & Pharmacy
Paul T. Winnard, Farhad Vesuna, Venu Raman
Summary: DDX3X, a multifunctional protein utilized by various viruses, plays a crucial role in viral metabolism. Modulating the functions of DDX3 during viral infections could effectively suppress viral production and have a significant impact on safely and efficiently subduing a broad spectrum of viral infections.
ANTIVIRAL RESEARCH
(2021)
Article
Orthopedics
Peng Zhao, Guobin Ma, Lintong Ma
Summary: The study found that miR-181a-5p plays an important role in osteoarthritis by regulating DDX3X to alleviate inflammation, suggesting it as a potential therapeutic target for the treatment of human osteoarthritis.
JOURNAL OF ORTHOPAEDIC SURGERY AND RESEARCH
(2023)
Article
Oncology
Andrew B. Lassman, Patrick Y. Wen, Martin J. van den Bent, Scott R. Plotkin, Annemiek M. E. Walenkamp, Adam L. Green, Kai Li, Christopher J. Walker, Hua Chang, Sharon Tamir, Leah Henegar, Yao Shen, Mariano J. Alvarez, Andrea Califano, Yosef Landesman, Michael G. Kauffman, Sharon Shacham, Morten Mau-Sorensen
Summary: In patients with glioblastoma, single-agent Selinxor therapy achieved intratumoral penetration and demonstrated some efficacy with manageable side effects. Importantly, the dosage of Selinxor needs to be adjusted based on patient tolerability.
CLINICAL CANCER RESEARCH
(2022)
Article
Microbiology
Thomas Kehrer, Anastasija Cupic, Chengjin Ye, Soner Yildiz, Mehdi Bouhaddou, Nicholas A. Crossland, Erika A. Barrall, Phillip Cohen, Anna Tseng, Tolga Cagatay, Raveen Rathnasinghe, Daniel Flores, Sonia Jangra, Fahmida Alam, Ignacio Mena, Sadaf Aslam, Anjali Saqi, Magdalena Rutkowska, Manisha R. Ummadi, Giuseppe Pisanelli, R. Blake Richardson, Ethan C. Veit, Jacqueline M. Fabius, Margaret Soucheray, Benjamin J. Polacco, Baran Ak, Arturo Marin, Matthew J. Evans, Danielle L. Swaney, Ana S. Gonzalez-Reiche, Emilia M. Sordillo, Harm van Bakel, Viviana Simon, Lorena Zuliani-Alvarez, Beatriz M. A. Fontoura, Brad R. Rosenberg, Nevan J. Krogan, Luis Martinez-Sobrido, Adolfo Garcia-Sastre, Lisa Miorin
Summary: The ORF6 protein of SARS-CoV-2 plays a crucial role in antagonizing the host's innate immunity by disrupting nuclear import and inhibiting cellular mRNA export. It also regulates viral protein expression. Mutations in ORF6 affect its interactions with host components and impair immune evasion in certain variants.
CELL HOST & MICROBE
(2023)
Article
Multidisciplinary Sciences
Matheus de Castro Fonseca, Juliana Ferreira de Oliveira, Bruno Henrique Silva Araujo, Camila Canateli, Paula Favoretti Vital do Prado, Dionisio Pedro Amorim Neto, Beatriz Pelegrini Bosque, Paulla Vieira Rodrigues, Joao Vitor Pereira de Godoy, Katiane Tostes, Helder Veras Ribeiro Filho, Andrey Fabricio Ziem Nascimento, Angela Saito, Celisa Caldana Costa Tonoli, Fernanda Aparecida Heleno Batista, Paulo Sergio Lopes de Oliveira, Ana Carolina Figueira, Silvia Souza da Costa, Ana Cristina Victorino Krepischi, Carla Rosenberg, Harry Westfahl, Antonio Jose Roque da Silva, Kleber Gomes Franchini
Summary: Current studies estimate that 1-3% of females with unexplained intellectual disability present de novo mutations in the DDX3X protein. The ID-linked missense mutation L556S in DDX3X may lead to protein misfolding and aggregation, compromising cell function. The cellular and molecular mechanisms by which DDX3X mutations impair brain development are not fully comprehended.
Review
Biochemistry & Molecular Biology
Steven M. Heaton, Paul R. Gorry, Natalie A. Borg
Summary: Antiretroviral therapy (ART) is effective in reducing HIV-1 infection. However, the emergence of treatment-refractory variants remains a challenge. HIV-1 uses cellular helicases, including DDX3X, to facilitate its replication. Exploring these helicases may reveal new therapeutic targets and help prevent viral escape.
TRENDS IN MICROBIOLOGY
(2023)
Article
Biology
Mariah L. Hoye, Lorenzo Calviello, Abigail J. Poff, Nna-Emeka Ejimogu, Carly R. Newman, Maya D. Montgomery, Jianhong Ou, Stephen N. Floor, Debra L. Silver
Summary: Mutations in the DDX3X gene play a crucial role in cortical development and are associated with DDX3X syndrome. The study shows that DDX3X controls translational and cell cycle control of neural progenitors, influencing neurogenesis and cortical development.
Article
Genetics & Heredity
Michael J. Cargill, Alicia Morales, Shashidhar Ravishankar, Edus H. Warren
Summary: Recent studies have shown that DDX3X accumulates at sites of DNA damage in the nucleus rapidly after induction, and its recruitment is mediated by its intrinsically disordered domains, similar to other RNA binding proteins. Inhibition of liquid-liquid phase separation also reduces DDX3X recruitment.
Article
Biochemistry & Molecular Biology
Amrita Sule, Sarah E. Golding, Syed F. Ahmad, James Watson, Mostafa H. Ahmed, Glen E. Kellogg, Tytus Bernas, Sean Koebley, Jason C. Reed, Lawrence F. Povirk, Kristoffer Valerie
Summary: Ataxia telangiectasia mutated (ATM) is a key regulator of the DNA damage response (DDR) and plays a crucial role in the phosphorylation of the structural subunit A (PR65-S401) of protein phosphatase 2A (PP2A). Phosphorylation of PR65-S401 by ATM controls diverse cellular processes such as mitosis and cell growth, as well as the recovery from DNA damage. The study showed that mutations in S401 of PR65 resulted in chromosomal aberrations, impaired DNA double-strand break repair, and increased mitotic catastrophe after radiation.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Pharmacology & Pharmacy
Fabiola Ciccosanti, Martina Di Rienzo, Alessandra Romagnoli, Francesca Colavita, Giulia Refolo, Concetta Castilletti, Chiara Agrati, Annalaura Brai, Fabrizio Manetti, Lorenzo Botta, Maria Rosaria Capobianchi, Giuseppe Ippolito, Mauro Piacentini, Gian Maria Fimia
Summary: The study characterized the interaction between host proteins and SARS-CoV-2 Nucleoprotein in infected cells, identifying key proteins involved in RNA metabolism and translation. It revealed the virus's manipulation of stress granule machinery for replication.
ANTIVIRAL RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
M. R. Heerma van Voss, F. Vesuna, G. M. Bol, J. Afzal, S. Tantravedi, Y. Bergman, K. Kammers, M. Lehar, R. Malek, M. Ballew, N. ter Hoeve, D. Abou, D. Thorek, C. Berlinicke, M. Yazdankhah, D. Sinha, A. Le, R. Abrahams, P. T. Tran, P. J. van Diest, V. Raman
Article
Oncology
Marise R. Heerma van Voss, Kai Kammers, Farhad Vesuna, Justin Brilliant, Yehudit Bergman, Saritha Tantravedi, Xinyan Wu, Robert N. Cole, Andrew Holland, Paul J. van Diest, Venu Raman
TRANSLATIONAL ONCOLOGY
(2018)
Article
Oncology
Saritha Tantravedi, Farhad Vesuna, Paul T. Winnard, Allison Martin, Michael Lim, Charles G. Eberhart, Cynthia Berlinicke, Eric Raabe, Paul J. van Diest, Venu Raman
TRANSLATIONAL ONCOLOGY
(2019)
Article
Immunology
Cesar Lopez-Camacho, Giuditta De Lorenzo, Jose Luis Slon-Campos, Stuart Dowall, Peter Abbink, Rafael A. Larocca, Young Chan Kim, Monica Poggianella, Victoria Graham, Stephen Findlay-Wilson, Emma Rayner, Jennifer Carmichael, Wanwisa Dejnirattisai, Michael Boyd, Roger Hewson, Juthathip Mongkolsapaya, Gavin R. Screaton, Dan H. Barouch, Oscar R. Burrone, Arvind H. Patel, Arturo Reyes-Sandoval
Article
Virology
Giuditta De Lorenzo, Rapeepat Tandavanitj, Jennifer Doig, Chayanee Setthapramote, Monica Poggianella, Ricardo Sanchez-Velazquez, Hannah E. Scales, Julia M. Edgar, Alain Kohl, James Brewer, Oscar R. Burrone, Arvind H. Patel
Summary: The study developed ZIKV subunit and virus-like particle (VLP)-based vaccines, which induced antibodies with a higher capacity to neutralize virus infection and protected animals from lethal challenge with both the African and Asian lineages of ZIKV. The engineered immunogens reduced the potential to induce antibody-dependent enhancement (ADE) of infection and showed promising efficacy in comparison with the wild-type derivatives.
JOURNAL OF VIROLOGY
(2021)
Review
Pharmacology & Pharmacy
Paul T. Winnard, Farhad Vesuna, Venu Raman
Summary: DDX3X, a multifunctional protein utilized by various viruses, plays a crucial role in viral metabolism. Modulating the functions of DDX3 during viral infections could effectively suppress viral production and have a significant impact on safely and efficiently subduing a broad spectrum of viral infections.
ANTIVIRAL RESEARCH
(2021)
Article
Multidisciplinary Sciences
Paul T. Winnard, Farhad Vesuna, Sankar Muthukumar, Venu Raman
Article
Cell Biology
Farhad Vesuna, Ala Lisok, Paul van Diest, Venu Raman
Summary: This study demonstrates that Twist upregulates the expression of miR-22 to decrease ER expression in breast cancer, with a direct correlation between Twist and miR-22 expression and increased breast cancer grade. MiR-22 regulates ER expression by binding to specific target sites, indicating a novel pathway for ER suppression in breast cancer.
MOLECULAR AND CELLULAR BIOCHEMISTRY
(2021)
Article
Virology
Theodorus J. Meuleman, Vanessa M. Cowton, Arvind H. Patel, Rob M. J. Liskamp
Summary: The article explores a chemistry-based approach towards fully synthetic peptide-based vaccine design, focusing on epitope mimicry of highly effective and conserved amino acid sequences in HCV-E2 glycoprotein. The cyclic epitope mimics assembled on an orthogonally protected scaffold were assessed in immunization experiments to investigate their potential in eliciting anti-HCV-E2 glycoprotein antibodies.
Article
Oncology
Praveen D. Sudhindar, Daniel Wainwright, Santu Saha, Rachel Howarth, Misti McCain, Yvonne Bury, Sweta S. Saha, Stuart McPherson, Helen Reeves, Arvind H. Patel, Geoffrey J. Faulkner, John Lunec, Ruchi Shukla
Summary: Chronic hepatitis C virus infection can activate L1 retrotransposons, potentially contributing to hepatocellular carcinoma development in patients with active or cleared viral infection. The study suggests a novel pathway for liver cancer development in chronic HCV patients.
Article
Virology
Vanessa M. Cowton, James Dunlop, Sarah J. Cole, Rachael E. Swann, Arvind H. Patel
Summary: Hepatitis C virus (HCV) infection is a major global health problem. Understanding the difference between antibody responses in individuals who naturally clear HCV infection and those who develop chronic infection is crucial for vaccine design. A study found that the neutralizing antibody response does not determine the outcome of HCV infection.
Article
Cell Biology
Farhad Vesuna, Marie-France Penet, Noriko Mori, Zaver M. Bhujwalla, Venu Raman
Summary: This study found that the Twist gene upregulates choline kinase expression in breast cancer cells through downregulation of FOXA1, resulting in the generation of an aggressive breast cancer phenotype.
MOLECULAR AND CELLULAR BIOCHEMISTRY
(2023)
Article
Microbiology
Farhad Vesuna, Ivan Akhrymuk, Amy Smith, Paul T. Winnard Jr, Shih-Chao Lin, Lauren Panny, Robert Scharpf, Kylene Kehn-Hall, Venu Raman
Summary: SARS-CoV-2 continues to spread globally, with evolving variants that are more transmissive and show reduced vaccine efficacy. Targeting host proteins such as DDX3 with RK-33 can effectively reduce viral load and downregulate SARS-CoV-2 genes, making it a potential strategy to control infection.
FRONTIERS IN MICROBIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Paulo Ricardo da Silva Sanches, Ricardo Sanchez-Velazquez, Mariana Nogueira Batista, Bruno Moreira Carneiro, Cintia Bittar, Giuditta De Lorenzo, Paula Rahal, Arvind H. Patel, Eduardo Maffud Cilli
Summary: Re-emerging arboviruses, particularly the Zika virus outbreak in South and Central America, pose a serious health threat in urban tropical areas. In this study, a peptide derived from human blood serum, Gallic acid-Hecate, was shown to effectively inhibit the replication of Zika virus in cultured cells. One of the synthesized metabolites of Gallic acid-Hecate, GA-metabolite 5, demonstrated the highest inhibitory activity against two strains of Zika virus. Furthermore, GA-metabolite 5 did not affect cell growth, making it a promising candidate for the development of antiviral drugs.
Meeting Abstract
Oncology
Patricia E. Berg, Yan-gao Man, Samuels Simmens, Sidney W. Fu, Lucianne Cavalli, Farhad Vesuna, Saurabh Kirolikar, Arnold Schwartz
MOLECULAR CANCER RESEARCH
(2018)