Browsing by Subject "Gene transcription"

Now showing 1 - 4 of 4
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    Healthy Women Have Higher Systemic Uromodulin Levels: Identification of Uromodulin as an Estrogen Responsive Gene
    (Wolters Kluwer, 2023) Nanamatsu, Azuma; Micanovic, Radmila; Khan, Shehnaz; El-Achkar, Tarek M.; LaFavers, Kaice A.; Medicine, School of Medicine
    *Serum uromodulin levels are higher in healthy female participants than healthy male participants. *Serum uromodulin levels in participants with normal kidney function do not correlate with eGFR but do correlate with body mass index. *Estrogen increases uromodulin production, likely because of noncanonical and half estrogen response elements in the UMOD gene.
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    HIPK2 directs cell type-specific regulation of STAT3 transcriptional activity in Th17 cell differentiation
    (National Academy of Science, 2022) Cheung, Ka Lung; Jaganathan, Anbalagan; Hu, Yuan; Xu, Feihong; Lejeune, Alannah; Sharma, Rajal; Caescu, Cristina I.; Meslamani, Jamel; Vincek, Adam; Zhang, Fan; Lee, Kyung; Zaware, Nilesh; Qayum, Amina Abdul; Ren, Chunyan; Kaplan, Mark H.; He, John Cijiang; Xiong, Huabao; Zhou, Ming-Ming; Microbiology and Immunology, School of Medicine
    SignificanceSTAT3 (signal transducer and activator of transcription 3) is a master transcription factor that organizes cellular responses to cytokines and growth factors and is implicated in inflammatory disorders. STAT3 is a well-recognized therapeutic target for human cancer and inflammatory disorders, but how its function is regulated in a cell type-specific manner has been a major outstanding question. We discovered that Stat3 imposes self-directed regulation through controlling transcription of its own regulator homeodomain-interacting protein kinase 2 (Hipk2) in a T helper 17 (Th17) cell-specific manner. Our validation of the functional importance of the Stat3-Hipk2 axis in Th17 cell development in the pathogenesis of T cell-induced colitis in mice suggests an approach to therapeutically treat inflammatory bowel diseases that currently lack a safe and effective therapy.
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    Phorbol ester induced ex vivo expansion of rigorously-defined phenotypic but not functional human cord blood hematopoietic stem cells: a cautionary tale demonstrating that phenotype does not always recapitulate stem cell function
    (Springer Nature, 2019-12) Chen, Yandan; Yao, Chunxu; Teng, Yincheng; Jiang, Rongzhen; Huang, Xinxin; Liu, Sheng; Wan, Jun; Broxmeyer, Hal E.; Guo, Bin; Microbiology and Immunology, School of Medicine
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    PuF, an antimetastatic and developmental signaling protein, interacts with the Alzheimer’s amyloid-β precursor protein via a tissue-specific proximal regulatory element (PRE)
    (Springer Nature, 2013-01-31) Lahiri, Debomoy K.; Maloney, Bryan; Rogers, Jack T.; Ge, Yuan-Wen; Psychiatry, School of Medicine
    Background: Alzheimer's disease (AD) is intimately tied to amyloid-β (Aβ) peptide. Extraneuronal brain plaques consisting primarily of Aβ aggregates are a hallmark of AD. Intraneuronal Aβ subunits are strongly implicated in disease progression. Protein sequence mutations of the Aβ precursor protein (APP) account for a small proportion of AD cases, suggesting that regulation of the associated gene (APP) may play a more important role in AD etiology. The APP promoter possesses a novel 30 nucleotide sequence, or "proximal regulatory element" (PRE), at -76/-47, from the +1 transcription start site that confers cell type specificity. This PRE contains sequences that make it vulnerable to epigenetic modification and may present a viable target for drug studies. We examined PRE-nuclear protein interaction by gel electrophoretic mobility shift assay (EMSA) and PRE mutant EMSA. This was followed by functional studies of PRE mutant/reporter gene fusion clones. Results: EMSA probed with the PRE showed DNA-protein interaction in multiple nuclear extracts and in human brain tissue nuclear extract in a tissue-type specific manner. We identified transcription factors that are likely to bind the PRE, using competition gel shift and gel supershift: Activator protein 2 (AP2), nm23 nucleoside diphosphate kinase/metastatic inhibitory protein (PuF), and specificity protein 1 (SP1). These sites crossed a known single nucleotide polymorphism (SNP). EMSA with PRE mutants and promoter/reporter clone transfection analysis further implicated PuF in cells and extracts. Functional assays of mutant/reporter clone transfections were evaluated by ELISA of reporter protein levels. EMSA and ELISA results correlated by meta-analysis. Conclusions: We propose that PuF may regulate the APP gene promoter and that AD risk may be increased by interference with PuF regulation at the PRE. PuF is targeted by calcium/calmodulin-dependent protein kinase II inhibitor 1, which also interacts with the integrins. These proteins are connected to vital cellular and neurological functions. In addition, the transcription factor PuF is a known inhibitor of metastasis and regulates cell growth during development. Given that APP is a known cell adhesion protein and ferroxidase, this suggests biochemical links among cell signaling, the cell cycle, iron metabolism in cancer, and AD in the context of overall aging.