Although the protooncogene c-Jun plays a critical role in cell proliferation, cell death, and malignant transformation, DNA microarray screens have identified only a few human cancer types with aberrant expression of c-Jun. Here, we show that c-Jun accumulation is robustly elevated in human glioblastoma and that this increase contributes to the malignant properties of the cells. Most importantly, the increase in c-Jun protein accumulation occurs with no corresponding increase in c-Jun mRNA or the half-life of the c-Jun protein but, rather, in the translatability of the transcript. The c-Jun 5'UTR harbors a potent internal ribosomal entry site (IRES) with a virus-like IRES domain that directs cap-independent translation in glioblastoma cells. Accumulation of c-Jun is not dependent on MAPK activity but can be stimulated by a cytoskeleton-dependent pathway. Our findings provide evidence that human c-Jun is an IRES-containing cellular transcript that contributes to cancer development through translational activation. This previously undescribed mechanism of c-Jun regulation might also be relevant to other types of human cancer and offers unique potential targets for therapy.
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http://dx.doi.org/10.1073/pnas.1203659109 | DOI Listing |
Cancer Lett
January 2025
Department of Clinical Laboratory, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, PR China; Department of Clinical Laboratory, Xiasha Campus, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, PR China; Key Laboratory of Precision Medicine in Diagnosis and Monitoring Research of Zhejiang Province, Hangzhou, Zhejiang, PR China. Electronic address:
Fish Shellfish Immunol
January 2025
Jimei University, College of Fisheries, Key Laboratory of Healthy Mariculture for the East China Sea, Xiamen, 361021, China; Jimei University, College of Fisheries, Engineering Research Center of the Modern Technology for Eel Industry, Xiamen, 361021, China. Electronic address:
Fas-associated protein with Death Domain (FADD) is a crucial signaling component of apoptosis and a vital immunomodulator on inflammatory signaling pathways. However, information on FADD-mediated apoptosis and immune regulation is limited in teleost. We herein cloned a FADD homolog, AjFADD, from Japanese eel (Anguilla japonica).
View Article and Find Full Text PDFGene
January 2025
School of Life Sciences, Fudan University, Shanghai 200433, China; MOE Engineering Research Center of Gene Technology, School of Life Sciences, Obstetrics and Gynecology Hospital, Fudan University, Shanghai 200433, China. Electronic address:
Bisphenol A (BPA) is a widely used industrial compound commonly found in various everyday plastic products. Known for its endocrine-disrupting properties, BPA can enter the human body through multiple pathways. Prenatal exposure to BPA not only disrupts placental structure and function but also interferes with normal steroid metabolism.
View Article and Find Full Text PDFJ Ethnopharmacol
January 2025
Department of Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No.197 Ruijin 2nd Road, Shanghai 200025, China. Electronic address:
Ethnopharmacological Relevance: Yi-Shen-Hua-Shi granules (YSHSG) have been shown to improve kidney function in various renal disorders, which are characterized by the sudden decline and impairment of kidney function.
Aim Of The Study: To investigate the precise mechanisms and targets of YSHSG in combating sepsis-induced AKI.
Materials And Methods: Through network pharmacology, the active ingredients, main target proteins, and related signaling pathways of YSHSG in the treatment of sepsis-induced AKI were predicted.
Nat Commun
January 2025
Center for Research Informatics, The University of Chicago, Chicago, IL, USA.
The fallopian tube undergoes extensive molecular changes during the menstrual cycle and menopause. We use single-cell RNA and ATAC sequencing to construct a comprehensive cell atlas of healthy human fallopian tubes during the menstrual cycle and menopause. Our scRNA-seq comparison of 85,107 pre- and 46,111 post-menopausal fallopian tube cells reveals substantial shifts in cell type frequencies, gene expression, transcription factor activity, and cell-to-cell communications during menopause and menstrual cycle.
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