Prohibitins (PHBs) are ubiquitously expressed conserved proteins in eukaryotes that are associated with apoptosis, cancer formation, aging, stress responses and cell proliferation. However, the function of the PHBs in immune regulation has largely not been determined. In the present study, we identified PHB2 in the red swamp crayfish Procambarus clarkii. PHB2 was found to be widely distributed in several tissues, and its expression was significantly upregulated by white spot syndrome virus (WSSV) challenge. PHB2 significantly reduced the amount of WSSV in crayfish and the mortality of WSSV-infected crayfish. Here, we observed that PHB2 promotes the nuclear translocation of STAT by binding to STAT. After blocking PHB2 or STAT with antibodies or interfering with PHB2 or STAT, the expression levels of the antiviral genes β-thymosin (PcThy-4) and crustin2 (Cru2) decreased. The gene sequence of PHB2 was analyzed and found to contain a nuclear introgression sequence (NIS). After in vivo injection of PHB2 with deletion of NIS (rΔNIS-PHB2), the nuclear translocation of STAT did not change significantly compared to that in the control group. These results suggest that PHB2 promoted the nuclear translocation of STAT through NIS and mediated the expression of antiviral proteins to inhibit WSSV infection.
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http://dx.doi.org/10.1016/j.fsi.2024.109503 | DOI Listing |
Cell Mol Gastroenterol Hepatol
January 2025
Center for Advanced Biotechnology and Medicine, Rutgers University, Piscataway, NJ, USA. Electronic address:
Background & Aims: Erythropoietic protoporphyria (EPP) is caused by mutations in ferrochelatase which inserts iron into protoporphyrin-IX (PP-IX) to generate heme. EPP is characterized by PP-IX accumulation, skin photosensitivity, cholestasis, and end-stage liver disease. Despite available drugs that address photosensitivity, treatment of EPP-related liver disease remains an unmet need.
View Article and Find Full Text PDFBiochem Biophys Res Commun
January 2025
State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200032, China; Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China. Electronic address:
PIK3CA, which encodes protein p110α, is one of the most frequently mutated oncogenes and a promising drug-target for human cancer. Previously, we demonstrate that p85β is released from PI3K complex which contain PIK3CA helical domain mutations and translocates into nucleus to regulate tri-methylation of H3K27, thereby promoting tumorigenicity. Here, we identify DIRAS2 and SOWAHB as target genes of nuclear p85β in PIK3CA-helical-domain-mutant tumors.
View Article and Find Full Text PDFInt Immunopharmacol
January 2025
Pharmacology Division, Council of Scientific and Industrial Research-Indian Institute of Integrative Medicine, Jammu, Jammu and Kashmir 180001, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, Uttar Pradesh 201002, India. Electronic address:
Melanoma is an aggressive form of malignancy that originates from melanin-producing cells known as melanocytes underlying the basal layer of the epidermis with a poor prognosis, low survival rates, and limited treatment options. Although several specific and effective systematic strategies for treating melanoma have been established, the underlying molecular mechanism of melanoma progression, mortality and the promising therapeutic options remain elusive. Shikonin (SK), a natural naphthoquinone derived from a medicinal herbaceous plant, has been shown to inhibit the proliferation of several cancer cells.
View Article and Find Full Text PDFPLoS Pathog
January 2025
Institute of Pediatric Infection, Immunity, and Critical Care Medicine, Shanghai Children's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
IKKε is a traditional antiviral kinase known for positively regulating the production of type I interferon (IFN) and the expression of IFN-stimulated genes (ISGs) during various virus infections. However, through an inhibitor screen targeting cellular kinases, we found that IKKε plays a crucial role in the lytic replication of Kaposi's sarcoma-associated herpesvirus (KSHV). Mechanistically, during KSHV lytic replication, IKKε undergoes significant SUMOylation at both Lys321 and Lys549 by the viral SUMO E3 ligase ORF45.
View Article and Find Full Text PDFJ Immunol Res
January 2025
Department of Microbiology, Immunology and Genetics Faculty of Health Sciences, Ben Gurion University of the Negev, Beer Sheva 84105, Israel.
Inflammation is a critical response of the immune system to infection or injury, serving to repair and restore tissue homeostasis. While acute inflammation generally protects against harmful stimuli, prolonged and chronic inflammation have detrimental effects and disrupts tissue homeostasis. Due to the complex and multifactorial etiology of chronic inflammation, effective treatment remains elusive.
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