國家衛生研究院 NHRI:Item 3990099045/2174
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    Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/2174


    Title: Requirement for high mobility group protein HMGI-C interaction with STAT3 inhibitor PIAS3 in repression of a-subunit of epithelial Na+ channel (alpha-ENaC) transcription by Ras activation in salivary epithelial cells
    Authors: Zentner, MD;Lin, HH;Deng, HT;Kim, KJ;Shih, HM;Ann, DK
    Contributors: Division of Molecular and Genomic Medicine
    Abstract: Previously, we have demonstrated that oxidative stress or Ras/ERK activation leads to the transcriptional repression of alpha -subunit of epithelial Na+ channel (ENaC in lung and salivary epithelial cells. Here, we further investigated the coordinated molecular mechanisms by which alpha -ENaC expression is regulated. Using both stable and transient transfection assays, we demonstrate that the overexpression of high mobility group protein I-C (HMGI-C), a Ras/ERK-inducible HMG-I family member, represses glucocorticoid receptor (GR)/dexamethasone (Dex)-stimulated alpha -ENaC/reporter activity in salivary epithelial cells. Northern analyses further confirm that the expression of endogenous a-ENaC gene in salivary Pa-4 cells is suppressed by an ectopic HMGI-C overexpression. Through yeast two-hybrid screening and co-immunoprecipitation assays from eukaryotic cells, we also discovered the interaction between HMGI-C and PIAS3 (protein inhibitor of activated STAT3 (signal transducer and activator of transcription 3)). A low level of ectopically expressed PIAS3 cooperatively inhibits GR/Dex-dependent alpha -ENaC transcription in the presence of HMGI-C. Reciprocally, HMGI-C expression also coordinately enhances PIAS3-mediated repression of STAT3-dependent transactivation. Moreover, overexpression of antisense HMGI-C construct is capable of reversing the repression mediated by Ras V12 on GR- and STAT3-dependent transcriptional activation. Together, our results demonstrate that Ras/ERK-mediated induction of HMGI-C is required to effectively repress GR/Dex-stimulated transcription of alpha -ENaC gene and STAT3-mediated transactivation. These findings delineate a network of inhibitory signaling pathways that converge on HMGI-C.PIAS3 complex, causally associating Ras/ERK activation with the repression of both GR and STAT3 signaling pathways in salivary epithelial cells.
    Keywords: Biochemistry & Molecular Biology
    Date: 2001-08-10
    Relation: Journal of Biological Chemistry. 2001 Aug;276(32):29805-29814.
    Link to: http://dx.doi.org/10.1074/jbc.M103153200
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1083-351X&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000170558000028
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=0035839425
    Appears in Collections:[Hsiu-Ming Shih] Periodical Articles

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