Heat shock factor 1 (HSF1) is one of the most important transcriptional molecules in the heat shock process; however, HSF1 can also regulate the expression of other proteins. Dystrophin Dp71 is one of the most widely expressed isoforms of the dystrophin gene family. In our experiments, we showed for the first time that HSF1 can function as a transcriptional factor for endogenous Dp71 expression in vivo and in vitro. We demonstrated that the messenger RNA (mRNA) and protein expression of Dp71 were significantly reduced in HSF1-knockout mice compared with wild-type mice in brain, lung, liver, spleen, and kidney. Overexpression of HSF1 significantly enhanced the mRNA and protein expression of Dp71 in HeLa cells. Inhibiting the expression of HSF1 in HeLa cells significantly reduced the expression of Dp71. By use of the EMSA technique, the chromatin immunoprecipitation assay, and the luciferase reporter system, we demonstrated that HSF1 can directly bind the HSE in the Dp71 promoter region. We concluded from our data that HSF1 functions as a transcriptional regulator of Dp71 expression.
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http://dx.doi.org/10.1007/s12192-014-0558-8 | DOI Listing |
Brain
December 2024
Dubowitz Neuromuscular Centre, University College London, Great Ormond Street Institute of Child Health, London, WC1N 1EH, UK.
Dystrophin is a protein crucial for maintaining the structural integrity of skeletal muscle. So far, the attention was focused on the role of dystrophin in muscle in view of the devastating progression of weakness and early death that characterises Duchenne muscular dystrophy. However, in the last few years, the role of shorter dystrophin isoforms, including development and adult expression-specific mechanisms, has been a greater focus.
View Article and Find Full Text PDFNeurobiol Dis
September 2024
Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China; Institute of Stroke Research, Soochow University, Suzhou, Jiangsu Province, China.
Objective: The glymphatic system serves as a perivascular pathway that aids in clearing liquid and solute waste from the brain, thereby enhancing neurological function. Disorders in glymphatic drainage contribute to the development of vasogenic edema following cerebral ischemia, although the molecular mechanisms involved remain poorly understood. This study aims to determine whether a deficiency in dystrophin 71 (DP71) leads to aquaporin-4 (AQP4) depolarization, contributing to glymphatic dysfunction in cerebral ischemia and resulting in brain edema.
View Article and Find Full Text PDFHum Mol Genet
June 2024
School of Pharmacy and Biomedical Sciences, University of Portsmouth, White Swan Road, Portsmouth PO1 2DT, United Kingdom.
Alterations in Dp71 expression, the most ubiquitous dystrophin isoform, have been associated with patient survival across tumours. Intriguingly, in certain malignancies, Dp71 acts as a tumour suppressor, while manifesting oncogenic properties in others. This diversity could be explained by the expression of two Dp71 splice variants encoding proteins with distinct C-termini, each with specific properties.
View Article and Find Full Text PDFMol Neurobiol
December 2024
Departamento de Genética y Biología Molecular, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV), Mexico City, Mexico.
Dystrophin Dp71 is the major product of the Duchenne muscular dystrophy (DMD) gene in the brain, and its loss in DMD patients and mouse models leads to cognitive impairments. Dp71 is expressed as a range of proteins generated by alternative splicing of exons 71 to 74 and 78, classified in the main Dp71d and Dp71f groups that contain specific C-terminal ends. However, it is unknown whether each isoform has a specific role in distinct cell types, brain regions, and/or stages of brain development.
View Article and Find Full Text PDFTransl Lung Cancer Res
April 2024
Molecular Medicine Group, School of Pharmacy and Biomedical Sciences, University of Portsmouth, Portsmouth, UK.
Background: The identification of prognostic biomarkers is crucial for guiding treatment strategies in mesothelioma patients. The Duchenne muscular dystrophy () gene and its specific transcripts have been associated with patient survival in various tumours. In this study, we aimed to investigate the prognostic potential of gene expression and its transcripts in mesothelioma patients.
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