Li Zou

Nanjing Medical University, Nan-ching, Jiangsu Sheng, China

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Publications (5)13.06 Total impact

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    ABSTRACT: CD2-associated protein (CD2AP) is an adaptor molecule involved in T cell receptor signaling and podocyte homeostasis. CD2AP-deficient mice develop nephritic syndrome and renal failure caused by glomerulosclerosis. Transcription factor E2F1 is a key regulator of cell proliferation and apoptosis. Here we report that E2F1 up-regulates the human CD2AP promoter and further increases the mRNA and protein levels of the human CD2AP in human embryonic kidney (HEK) 293 cells. By semi-quantitative RT-PCR and Western blot analysis we demonstrate that ectopic expression of E2F1 elevates the mRNA and protein levels of CD2AP. Consistently, transient transfection assays prove that overexpression of E2F1 transactivates the CD2AP promoter while knocking-down of endogenous E2F1 by a shRNA strategy results in reduction of the CD2AP promoter activity. Toward understanding the underlying mechanism of this regulation, we performed chromatin immunoprecipitation and mutations of the putative Sp1 binding sites, demonstrating that E2F1 can bind to Sp1 binding site and overexpression of E2F1 is capable of increasing the binding of E2F1 and decreasing the binding of Sp1 to Sp1 binding sites.
    PLoS ONE 08/2012; 7(8):e42774. DOI:10.1371/journal.pone.0042774 · 3.53 Impact Factor
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    ABSTRACT: Interferon regulatory factor 3 (IRF-3) plays a crucial role in initiation and development of the IFN antiviral response. The expression level of human IRF-3 is thought to be closely related to antiviral state of cells. However, the mechanisms of the transcription regulation of IRF-3 have remained largely unknown. We previously reported that transcription factor E2F1 negatively regulates the basal transcriptional activity of IRF-3. Here we demonstrate that transcription factors Sp1 and Sp3 up-regulate the basal transcriptional activity of IRF-3 and increase IRF-3 expression at mRNA level. By transient transfection analysis we revealed that mutation of Sp1/NRF-1 binding site resulted in a profound reduction of IRF-3 promoter activity. Overexpression of Sp1 and Sp3, but not NRF-1, transactivated the IRF-3 promoter activity in reporter gene assays while knocking-down of endogenous Sp1 and Sp3 by a shRNA strategy markedly inhibited IRF-3 promoter activity. Chromatin immunoprecipitation (ChIP) assays showed that Sp1 and Sp3 interact with the IRF-3 promoter in vivo. These results suggest that basal expression level of IRF-3 is regulated by transcription factors Sp1 and Sp3.
    Biochimie 03/2012; 94(6):1390-7. DOI:10.1016/j.biochi.2012.03.011 · 3.12 Impact Factor
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    ABSTRACT: The CD2 associated protein (CD2AP) is characterized as a T-lymphocyte CD2 adapter protein and is found to be related to glomerulosclerosis, and CD2AP knockout mice develop a rapid onset nephrotic syndrome and die of renal failure. Here we report that the transcription factor Sp1 and Sp3 up-regulate the basal transcriptional activity of CD2AP and increase CD2AP expression at mRNA level. We show by Chromatin immunoprecipitation (ChIP) assay that Sp1 and Sp3 interact with the CD2AP promoter region in vivo. By transient transfection analysis we also demonstrate the mutations of Sp1/3 binding sites result in a profound reduction of CD2AP promoter activity. Overexpression of Sp1 and Sp3 transactivates the CD2AP promoter, whereas small interfering RNA-mediated (siRNA) blockage of Sp1 and Sp3 genes expressions inhibits markedly its activity. These results suggest that Sp1 and Sp3 play an important role in regulating CD2AP transcription through binding to the Sp1/3 binding sites.
    Molecular Biology Reports 05/2011; 39(2):1479-86. DOI:10.1007/s11033-011-0885-0 · 1.96 Impact Factor
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    ABSTRACT: Interferon regulatory factor 3 (IRF-3) plays an important role in virus and double-stranded RNA-mediated induction of type I interferon and RANTES, DNA damage signaling, tumor suppression, and virus-induced apoptosis. However, cis elements or trans factors responsible for regulating IRF-3 expression remain largely unknown. Here we report that the transcription factor E2F1 negatively regulates the basal transcriptional activity of IRF-3 and deregulates IRF-3 expression at mRNA level. By transient transfection analysis, we demonstrate that the mutation of E2F-binding site results in a profound promotion of IRF-3 promoter activity. Overexpression of E2F1, but not a mutant E2F1, represses the IRF-3 promoter activity in reporter gene assays while knocking down of endogenous E2F1 by shRNA strategy results in enhanced IRF-3 promoter activity. Electrophoretic gel mobility shift assays and antibody competition assays confirm that E2F1 protein binds to the E2F consensus binding site in the IRF-3 promoter. Chromatin immunoprecipitation assays demonstrate that E2F1 interacts with the IRF-3 promoter in vivo. These results suggest that E2F1 negatively regulates IRF-3 transcription through binding to the E2F consensus binding site.
    Immunogenetics 04/2011; 63(4):189-96. DOI:10.1007/s00251-010-0505-5 · 2.49 Impact Factor
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    ABSTRACT: Interferon regulatory factor 3 (IRF-3) is one of the master transcription factors involved in the stringent regulation of interferon production following virus infection. The aim of our study was to explore new isoforms of IRF-3 and further characterize transcriptional regulation. Two new TSSs of IRF-3 were identified by 5' RACE experiments. The expression profiles of new isoforms were tested using RT-PCR. Additionally, the promoter activity and potential transcription factor binding sites of the promoter regions were analyzed. Here we report two novel spliced variants of IRF-3 starting from intron 2 of the wild type of IRF-3, Int2V1 and Int2V2. We localized the transcription start sites (TSS) in the second intron of IRF-3 in pheochromocytoma tissue and thus identified two distinct transcripts. RT-PCR results showed they were expressed in most of tissues and cell lines tested. The expressions levels of them are varying in different tissues and cells. Furthermore, Int2V2 were expressed higher than Int2V1 in all tissues. Luciferase analysis in Hela and 293T cell line defined the promoter regions of the new transcripts had higher promoter activities. Both of the relative luciferase activities were over 100 times higher than that of pGL3-Basic vector. Bioinformatics analysis demonstrated that it contains Sp1, GATA-1/2, IRF-1/2 and Lyf-1 transcription factor binding sites in the promoter regions. The discovery of new transcripts of IRF-3 provides a further insight into the alternative splicing of IRF-3. The novel isoforms expanded the splice variants numbers of IRF-3.
    Molecular Biology Reports 12/2010; 38(7):4415-21. DOI:10.1007/s11033-010-0569-1 · 1.96 Impact Factor

Publication Stats

21 Citations
13.06 Total Impact Points

Institutions

  • 2010–2012
    • Nanjing Medical University
      • Department of Pediatrics
      Nan-ching, Jiangsu Sheng, China