Article
Immunology
Chen-Yang Liao, Cao-Qi Lei, Hong-Bing Shu
Summary: PCBP1 is an important factor in promoting cGAS activation and binding to viral DNA. Deficiency of PCBP1 can inhibit the innate immune response triggered by cytosolic DNA and DNA viruses.
CELLULAR & MOLECULAR IMMUNOLOGY
(2021)
Article
Multidisciplinary Sciences
Christina K. Baumgartner, Hakimeh Ebrahimi-Nik, Arvin Iracheta-Vellve, Keith M. Hamel, Kira E. Olander, Thomas G. R. Davis, Kathleen A. Mcguire, Geoff T. Halvorsen, Omar I. Avila, Chirag H. Patel, Sarah Y. Kim, Ashwin V. Kammula, Audrey J. Muscato, Kyle Halliwill, Prasanthi Geda, Kelly L. Klinge, Zhaoming Xiong, Ryan Duggan, Liang Mu, Mitchell D. Yeary, James C. Patti, Tyler M. Balon, Rebecca Mathew, Carey Backus, Domenick E. Kennedy, Angeline Chen, Kenton Longenecker, Joseph T. Klahn, Cara L. Hrusch, Navasona Krishnan, Charles W. Hutchins, Jax P. Dunning, Marinka Bulic, Payal Tiwari, Kayla J. Colvin, Cun Lan Chuong, Ian C. Kohnle, Matthew G. Rees, Andrew Boghossian, Melissa Ronan, Jennifer A. Roth, Meng-Ju Wu, Juliette S. M. T. Suermondt, Nelson H. Knudsen, Collins K. Cheruiyot, Debattama R. Sen, Gabriel K. Griffin, Todd R. Golub, Nabeel El-Bardeesy, Joshua H. Decker, Yi Yang, Magali Guffroy, Stacey Fossey, Patricia Trusk, Im-Meng Sun, Yue Liu, Wei Qiu, Qi Sun, Marcia N. Paddock, Elliot P. Farney, Mark A. Matulenko, Clay Beauregard, Jennifer M. Frost, Kathleen B. Yates, Philip R. Kym, Robert T. Manguso
Summary: Immune checkpoint blockade is effective but not for all cancer patients. This study introduces a first-in-class inhibitor, AC484, that targets the active site of phosphatases PTPN2 and PTPN1, promoting anti-tumor immunity and enhancing immune cell function. AC484 shows promising potential as a new strategy for cancer immunotherapy.
Review
Immunology
Yuhan Zhong, Xiao Zhong, Liangjun Qiao, Hong Wu, Chang Liu, Ting Zhang
Summary: The Z alpha domain is a compact α/β structure that specifically binds to nucleic acids with a left-handed helical conformation. It has been identified in several proteins, including ADAR1 and ZBP1, which play important roles in immune response regulation.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Takahisa Kouwaki, Tasuku Nishimura, Guanming Wang, Reiko Nakagawa, Hiroyuki Oshiumi
Summary: Post-translational modification of LGP2 fine-tunes antiviral innate immune responses by promoting late-phase expression of type I interferons, while attenuating other antiviral proteins.
Review
Virology
Valentina Budroni, Gijs A. Versteeg
Summary: The innate immune system is rapidly and dynamically activated through post-translational modifications of signaling molecules, ensuring efficient response to infections. After infection resolution, rapid proteome remodeling is required to prevent hyperactivation.
Article
Biochemistry & Molecular Biology
Yijie Tao, Shulei Yin, Yang Liu, Chunzhen Li, Yining Chen, Dan Han, Jingyi Huang, Sheng Xu, Zui Zou, Yizhi Yu
Summary: In this study, UFL1 was identified as a crucial regulator for maintaining the stability and antiviral function of STING. It inhibits the interaction between TRIM29 and STING, thereby reducing the ubiquitination and proteasomal degradation of STING. Additionally, DNA virus infection reduces the expression of UFL1, which may enhance STING degradation and viral expansion.
CELL DEATH AND DIFFERENTIATION
(2023)
Article
Virology
Nathan A. Krump, Ranran Wang, Wei Liu, June F. Yang, Tongcui Ma, Jianxin You
Summary: MCPyV, which can cause Merkel cell carcinoma, infects most humans asymptomatically. Understanding MCPyV biology and its interaction with host immune response may help develop targeted therapies for MCC. MCPyV replication induces an innate immune response, involving cGAS-STING, NF-kappa B, and IFI16 pathways.
JOURNAL OF VIROLOGY
(2021)
Article
Biochemistry & Molecular Biology
Jeffrey C. Hsiao, Atara R. Neugroschl, Ashley J. Chui, Cornelius Y. Taabazuing, Andrew R. Griswold, Qinghui Wang, Hsin-Che Huang, Elizabeth L. Orth-He, Daniel P. Ball, Giorgos Hiotis, Daniel A. Bachovchin
Summary: CARD8, a pattern-recognition receptor, is involved in the activation of the inflammasome. The degradation of CARD8 by the 20S proteasome plays a crucial role in the control of inflammasome activation.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Helena M. Schnell, Jessie Ang, Shaun Rawson, Richard M. Walsh, Yagmur Micoogullari, John Hanna
Summary: The proteasome, a complex responsible for protein degradation, has gates in its central core particle (CP) that control substrate access. These gates are opened by the regulatory particle (RP). Recent research has shown that the CP assembly chaperones Pba1/2 can also mediate gate opening through a unique structural arrangement. In this study, a detailed analysis of CP gate modulation by Pba1/2 was conducted, revealing that Pba1/2 can regulate the gates through direct interactions and disrupt the closed state. This novel mechanism appears to be specific to Pba1/2 and occurs during proteasome assembly.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Dennis C. Koester, Vanessa M. Marx, Sarah Williams, Jan Jiricek, Maxime Dauphinais, Olivier Rene, Sarah L. Miller, Lei Zhang, Debjani Patra, Yen-Liang Chen, Harry Cheung, Jonathan Gable, Suresh B. Lakshminarayana, Colin Osborne, Jean-Rene Galarneau, Upendra Kulkarni, Wendy Richmond, Angela Bretz, Linda Xiao, Frantisek Supek, Christian Wiesmann, Srinivas Honnappa, Celine Be, Pascal Maeser, Marcel Kaiser, Ryan Ritchie, Michael P. Barrett, Thierry T. Diagana, Christopher Sarko, Srinivasa P. S. Rao
Summary: This study presents a brain-penetrant, parasite-selective 20S proteasome inhibitor for the treatment of Human African Trypanosomiasis. The study utilized cryo-electron microscopy and an in silico model to guide hit expansion and lead optimization. In vitro and in vivo experiments successfully identified compounds with potential to cure the disease.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Review
Virology
Yixuan Wang, Wenwei Shao
Summary: Viral vectors play a crucial role in gene therapy, but the innate immune response remains a significant barrier to their clinical development. This review provides insights into the mechanisms of innate immune response induced by three widely used viral vectors and strategies to overcome innate immunity.
Review
Biochemistry & Molecular Biology
Thomas J. Hayman, Peter M. Glazer
Summary: Research on disease treatment has focused on DNA repair pathways, with potential for enhanced efficacy with novel immunotherapies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Virology
Jorge Rodrigues de Sousa, Raimunda do Socorro da Silva Azevedo, Juarez Antonio Simoes Quaresma, Pedro Fernando da Costa Vasconcelos
Summary: Zika virus, discovered in 1947 in Uganda, is an enveloped, positive-sense, single-stranded RNA virus. The Zika-epidemic in Brazil in 2015 was mainly characterized by the exponential growth of microcephaly cases and other congenital defects. Understanding the role of the immune response in the pathogenesis of ZIKV infection presents a challenge.
REVIEWS IN MEDICAL VIROLOGY
(2021)
Article
Biochemistry & Molecular Biology
Saayak Halder, Nathaniel J. Macatangay, Breanna L. Zerfas, Andres F. Salazar-Chaparro, Darci J. Trader
Summary: A series of oleic acid amide derivatives were synthesized to increase the protein degradation rate via the ubiquitin-independent pathway. These compounds were tested and compared to AM-404 in biochemical and cell-based assays. One of the molecules showed similar enhancement of the 20S CP activity as AM-404, but still caused unwanted cytotoxicity.
RSC MEDICINAL CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Yuexiu Zhang, Li-Sheng Zhang, Qing Dai, Phylip Chen, Mijia Lu, Elizabeth L. Kairis, Valarmathy Murugaiah, Jiayu Xu, Rajni Kant Shukla, Xueya Liang, Zhongyu Zou, Estelle Cormet-Boyaka, Jianming Qiu, Mark E. Peeples, Amit Sharma, Chuan He, Jianrong Li
Summary: The role of RNA m(5)C methylation in innate immunity against viruses has been explored. Depletion of NSUN2, an m(5)C methyltransferase, inhibits viral replication and gene expression through enhancing the type I interferon response. NSUN2 depletion reduces m(5)C methylation of noncoding RNAs (ncRNAs), leading to their upregulation and stimulating the IFN response. These findings suggest that RNA m(5)C methylation controls antiviral innate immunity.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
