Article
Microbiology
Nicole Brimer, Scott Vande Pol
Summary: This study reveals that the enhanced competitiveness of HPV16-infected cells is primarily due to the expression of the E6 oncoprotein, rather than the E7 or E5 oncoproteins. E6 can induce a super-competitor phenotype, which has important implications for understanding the mechanism of cell competition.
Article
Virology
Marcel Chris Conrady, Irina Suarez, Gergo Gogl, Desiree Isabella Frecot, Anna Bonhoure, Camille Kostmann, Alexandra Cousido-Siah, Andre Mitschler, JiaWen Lim, Murielle Masson, Thomas Iftner, Frank Stubenrauch, Gilles Trave, Claudia Simon
Summary: The study compared the structures and efficiency of ternary complex formation between oncogenic E6 proteins of closely related high-risk HPV31 and HPV16 with their cellular targets p53 and E6AP. Despite high structural similarity, 31 E6 showed an overall lower binding affinity than 16 E6, aligning with the observed lower p53 degradation potential of 31 E6.
JOURNAL OF VIROLOGY
(2021)
Article
Multidisciplinary Sciences
Lilian Esmeralda Araujo-Arcos, Suite Montano, Ciresthel Bello-Rios, Olga Lilia Garibay-Cerdenares, Marco Antonio Leyva-Vazquez, Berenice Illades-Aguiar
Summary: The oncogenic protein E6 from Human Papilloma Virus 16 (HPV-16) degrades Membrane-associated guanylate kinase with inverted domain structure-1 (MAGI-1) by binding with its PDZ1 domain. Variations in the E6 gene can modify the interaction between E6 and MAGI-1. MAGI-1 is a scaffolding protein found at tight junctions of epithelial cells and regulates signaling pathways. Through computational simulations and protein-protein docking, we found that specific variants have increased affinity to MAGI-1.
SCIENTIFIC REPORTS
(2022)
Article
Oncology
Jiajian Wang, Jie Dong, Yinjian Zhou, Kaiyi Wang, Min Pan, Zaixing Deng, Pengfei Wang, Ying Du, Weiguo Lu
Summary: This study aimed to assess the clinical performance of an HPV E6/E7 mRNA assay (Aptima HPV, AHPV) and AHPV 16 18/45 genotype assay (AHPV-GT) combined with age stratification for triaging women with atypical squamous cells of undetermined significance (ASC-US) cytology. The results showed that AHPV testing with age stratification is effective for triaging women with ASC-US cytology, and AHPV-GT testing may be a proper risk stratification method for women with AHPV-positive ASC-US cytology.
GYNECOLOGIC ONCOLOGY
(2022)
Article
Microbiology
Ramon Antano-Arias, Oscar Del Moral-Hernandez, Julio Ortiz-Ortiz, Luz Del Carmen Alarcon-Romero, Jorge Adan Navor-Hernandez, Marco Antonio Leyva-Vazquez, Marco Antonio Jimenez-Lopez, Jorge Organista-Nava, Berenice Illades-Aguiar
Summary: This study identified specific E7 variants associated with the highest risk of cervical cancer, with E6/E7 bicistron analysis revealing even greater risk potential for specific variants. These findings underscore the importance of analyzing combinations of E6/E7 variants in HPV 16 infection for predicting cervical cancer development.
Article
Biochemistry & Molecular Biology
Diego Carrillo-Beltran, Julio C. Osorio, Rances Blanco, Carolina Oliva, Enrique Boccardo, Francisco Aguayo
Summary: Although epidemiological studies suggest that tobacco smoking and HR-HPV infection are mutually exclusive risk factors for developing HNC, some individuals are both HPV-positive and smokers. Both factors increase oxidative stress and DNA damage. This study found that oral cells expressing HPV16 E6/E7 oncoproteins exposed to cigarette smoke condensate showed synergistic increases in SOD2 levels and DNA damage, independent of Akt1 and ATM. These findings suggest that the interaction between HPV and cigarette smoke in HNC promotes SOD2 alterations, leading to increased DNA damage and the development of a distinct clinical entity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Virology
Christine Kottaridi, Panagiota Resta, Danai Leventakou, Katerina Gioti, Ioannis Zygouras, Alina-Roxani Gouloumi, Georgios Sakagiannis, Khalid J. Alzahrani, Maria S. Venetikou, Fragkiski Anthouli-Anagnostopoulou, Apostolos Beloukas
Summary: Recent trends show a significant increase in the incidence of oropharyngeal squamous cell carcinoma associated with high-risk HPV type 16. However, there is limited published data on the genetic variations of this HPV type in oropharyngeal cancer. In this study, the genetic variations of HPV16 E6 gene sequences from a small cohort of Greek patients diagnosed with oropharyngeal cancer were assessed. The majority of sequences belonged to the European variant branch, with the T350G variation being the most predominant. Further studies are needed to explain the potential impact of this variation in the pathomechanisms of oropharyngeal cancer.
Article
Virology
Kerry Dust, Michael Carpenter, Julie Chih-yu Chen, Chris Grant, Stuart McCorrister, Garret R. Westmacott, Alberto Severini
Summary: This study investigates the effects of HPV16 viral proteins E6 and E7 on the host proteome in human neonatal keratinocytes. The results show that the expression of E6 and E7 leads to dysregulation in pathways related to interferon response, inflammation, and DNA damage repair. The study also identifies potential biomarkers associated with HPV oncoproteins in primary keratinocytes.
Article
Pharmacology & Pharmacy
Anbuselvam Mohan, Sneha Krishnamoorthy, Rajalakshmi Sabanayagam, Gregory Schwenk, Eric Feng, Hai-Feng Ji, Sridhar Muthusami
Summary: This study identified potential inhibitors for HPV16 E6 using pharmacophore-based virtual screening, molecular docking, ADME prediction and molecular dynamics simulation, and validated the efficacy of two compounds in regulating cervical cancer cells.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2023)
Article
Microbiology
Hye Seon Lee, Hye-Yeoung Yun, Eun-Woo Lee, Ho-Chul Shin, Seung Jun Kim, Bonsu Ku
Summary: The high-risk genotypes of human papillomaviruses (HPVs) are associated with cellular hyperproliferation abnormalities, including cervical cancer. In this study, it was demonstrated for the first time that the PDZ domain of human PTPN4 directly interacts with the PBM of HPV16 E6, providing structural and biochemical evidence for this interaction.
JOURNAL OF MICROBIOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Michael R. Bergman, Sophia A. Hernandez, Caitlin Deffler, Jingjie Yeo, Leila F. Deravi
Summary: This study investigates the role and interactions of crystallins in the lens and their impact on transparency. By studying crystallin combinations and properties, it was found that beta-crystallins play a crucial role in maintaining lens transparency. These findings contribute to the design of new transparent materials and enhance understanding of transparency regulation mechanisms.
Article
Biology
Jeffrey B. S. Gaither, Grant E. Lammi, James L. Li, David M. Gordon, Harkness C. Kuck, Benjamin J. Kelly, James R. Fitch, Peter White
Summary: Research suggests that synonymous variants may play a role in genetic disorders by disrupting mRNA structure. Tools have been developed to assess the impact of synonymous variants on mRNA structure, and a Structural Predictivity Index has been proposed to quantify this constraint.
Article
Medicine, Research & Experimental
Vaibhav Chand, Abhijeet Kapoor, Suman Kundu, Alo Nag
Summary: The aim of this study was to identify the interaction interface between hADA3 and HPV16E6 and design inhibitory peptides to disrupt the interaction. The designed peptide was found to impede the interaction and inhibit the malignant properties of cervical cancer cells. Intervention of the hADA3-E6 interaction holds promise as a potential strategy to treat HPV-induced cancers.
Article
Plant Sciences
Sho Furumura, Taro Ozaki, Akihiro Sugawara, Yohei Morishita, Kento Tsukada, Tatsuya Ikuta, Asuka Inoue, Teigo Asai
Summary: By mining fungal genomic information, a non-canonical iterative type I PKS with an N-terminal adenylation-thiolation didomain was found to catalyze the formation of naringenin chalcone. Analysis suggested the involvement of a C-terminal thioesterase domain in Claisen-type cyclization. Furthermore, an enzyme responsible for the biosynthesis of (2S)-flavanone in fungal flavonoids was also identified. These findings reveal novel fungal biosynthetic processes leading to plant-like metabolites.
JOURNAL OF NATURAL PRODUCTS
(2023)
Article
Biochemistry & Molecular Biology
Qiong Fan, Ting Huang, Xiao Sun, Yi-Wei Wang, Jing Wang, Yao Liu, Ting Ni, Sheng-Lan Gu, Yu-Hong Li, Yu-Dong Wang
Summary: Our study reveals that HPV-16 E6 can upregulate APOBEC3B expression in cervical cancer cells by directly binding to its promoter, leading to enhanced proliferation and hypomethylation of CCND1. This suggests that APOBEC3B may serve as a potential therapeutic target in human cervical cancer.
MOLECULAR CARCINOGENESIS
(2021)
Article
Multidisciplinary Sciences
Patrick Y. Sips, Xu Shi, Gabriel Musso, Anjali K. Nath, Yanbin Zhao, Jason Nielson, Jordan Morningstar, Amy E. Kelly, Brittney Mikell, Eva Buys, Vikhyat Bebarta, Jared Rutter, V. Jo Davisson, Sari Mahon, Matthew Brenner, Gerry R. Boss, Randall T. Peterson, Robert E. Gerszten, Calum A. MacRae
Article
Cell Biology
Remah Ali, Wells Brown, Stephen Connor Purdy, V. Jo Davisson, Michael K. Wendt
CELL DEATH & DISEASE
(2018)
Article
Chemistry, Medicinal
Aaron Lindstrom, Manu Anantpadma, Logan Baker, N. M. Raghavendra, Robert Davey, Vincent Jo Davisson
Article
Chemistry, Multidisciplinary
Matthew D. Bartolowits, Jonathon M. Gast, Ashlee J. Hasler, Anthony M. Cirrincione, Rachel J. O'Connor, Amr H. Mahmoud, Markus A. Lill, Vincent Jo Davisson
Article
Multidisciplinary Sciences
Jason R. Nielson, Anjali K. Nath, Kim P. Doane, Xu Shi, Jangwoen Lee, Emily G. Tippetts, Kusumika Saha, Jordan Morningstar, Kevin G. Hicks, Adriano Chan, Yanbin Zhao, Amy Kelly, Tara B. Hendry-Hofer, Alyssa Witeof, Patrick Y. Sips, Sari Mahon, Vikhyat S. Bebarta, Vincent Jo Davisson, Gerry R. Boss, Jared Rutter, Calum A. MacRae, Matthew Brenner, Robert E. Gerszten, Randall T. Peterson
Summary: Cyanide acts as a metabolic poison by inhibiting cytochrome c oxidase and other metabolic enzymes, causing metabolic perturbations. Glyoxylate has been identified as a potential cyanide countermeasure that can effectively and rapidly mitigate cyanide toxicity in animal models.
SCIENTIFIC REPORTS
(2022)
Article
Chemistry, Medicinal
Caroline B. Plescia, Aaron R. Lindstrom, Maritza Quintero, Patrick Keiser, Manu Anantpadma, Robert Davey, Robert Stahelin, V. Jo Davisson
Summary: The study reports the inhibition of Ebola virus cell entry by selectively inhibiting V-ATPase. The compounds show improved selectivity and minimal cytotoxicity.
ACS INFECTIOUS DISEASES
(2022)
Article
Medicine, General & Internal
Vallabh Suresh, Kaleb Byers, Ummadisetti Chinna Rajesh, Francesco Caiazza, Gina Zhu, Charles S. Craik, Kimberly Kirkwood, Vincent Jo Davisson, Daniel A. Sheik
Summary: The gastricsin activity assay developed in this study offers a rapid and accurate method for distinguishing between mucinous and non-mucinous pancreatic cyst fluids. The assay shows improvements in differentiation compared to standard ELISA assays and has a minimal impact on standard clinical care.
Article
Chemistry, Medicinal
Matthew M. Behymer, Huaping Mo, Naoaki Fujii, Vallabh Suresh, Adriano Chan, Jangweon Lee, Anjali K. Nath, Kusumika Saha, Sari B. Mahon, Matthew Brenner, Calum A. MacRae, Randall Peterson, Gerry R. Boss, Gregory T. Knipp, Vincent Jo Davisson
Summary: The use of platinum-based agents has shown promise in mitigating cyanide toxicity, both in vitro and in vivo. The addition of sulfur ligands enhances the cyanide scavenging properties of platinum and leads to robust and enhanced potency. These findings suggest a potential new lead for the development of next-generation cyanide countermeasures.
CHEMICAL RESEARCH IN TOXICOLOGY
(2022)
Article
Toxicology
Vik S. Bebarta, Xu Shi, Shunning Zheng, Tara B. Hendry-Hofer, Carter C. Severance, Matthew M. Behymer, Gerry R. Boss, Sari Mahon, Matthew Brenner, Gregory T. Knipp, Vincent Jo Davisson, Randall T. Peterson, Calum A. MacRae, Jared Rutter, Robert E. Gerszten, Anjali K. Nath
Summary: The study investigated the efficacy of intramuscular glyoxylate in a preclinical swine model of lethal cyanide poisoning. The results demonstrated that intramuscular administration of glyoxylate improved survival and clinical outcomes, and had positive effects on the biochemical effects of cyanide.
TOXICOLOGICAL SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Digambar Kumar Waiker, Akash Verma, Gajendra T. Akhilesh, T. A. Gajendra, Namrata Singh, Anima Roy, Hagera Dilnashin, Vinod Tiwari, Surendra Kumar P. Trigun, Surya P. Singh, Sairam Krishnamurthy, Prem Lama, Vincent Jo Davisson, Sushant Kumar Shrivastava
Summary: This study successfully designed and synthesized a new class of compounds for the treatment of Alzheimer's disease (AD) through a multitargeted directed ligand design approach. Compound 5d and 5f showed inhibitory activity against key enzymes involved in AD pathology and reduced the aggregation of Aβ. They also demonstrated neuroprotective effects and improved learning and memory behaviors in AD mouse models.
ACS CHEMICAL NEUROSCIENCE
(2023)
Article
Chemistry, Analytical
Vallabh Suresh, Daniel A. A. Sheik, Tyler C. C. Detomasi, Tianqi Zhao, Theresa Zepeda, Shyam Saladi, Ummadisetti Chinna Rajesh, Kaleb Byers, Charles S. S. Craik, Vincent Jo Davisson
Summary: With the shift of COVID-19 from pandemic to endemic, the focus of diagnostics will change from rapid detection to stratification for vulnerable patients. A fluorescent and Raman spectroscopic assay for SARS-CoV-2 3CL protease has been developed, which can be used sequentially with a fluorescent ACE2 activity measurement in the same sample. The prototype assay shows promising results in saliva, allowing non-invasive sampling and quick detection of ACE2 and 3CL protease activity.
Article
Chemistry, Multidisciplinary
Matthew D. Bartolowits, Meiguo Xin, Dino P. Petrov, Thomas J. Tague, Vincent Jo Davisson
Article
Biochemistry & Molecular Biology
Jordan Morningstar, Jangwoen Lee, Tara Hendry-Hofer, Alyssa Witeof, Tiffany Lyle, Gregg Knipp, Calum A. MacRae, Gerry R. Boss, Randall T. Peterson, Vincent J. Davisson, Robert E. Gerszten, Vikhyat S. Bebarta, Sari Mahon, Matt Brenner, Anjali K. Nath
Article
Biochemistry & Molecular Biology
Matthew D. Bartolowits, Wells Brown, Remah Ali, Anthony M. Pedley, Qingshou Chen, Kyle E. Harvey, Michael K. Wendt, Vincent Jo Davisson
ACS CHEMICAL BIOLOGY
(2017)
Article
Biochemistry & Molecular Biology
Kourtney M. Goode, Dino P. Petrov, Renee E. Vickman, Scott A. Crist, Pete E. Pascuzzi, Tim L. Ratliff, V. Jo Davisson, Tony R. Hazbun
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
(2017)