کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
9244075 | 1209899 | 2005 | 17 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
STAT3 NH2-Terminal Acetylation Is Activated by the Hepatic Acute-Phase Response and Required for IL-6 Induction of Angiotensinogen
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کلمات کلیدی
nEShAGTHAPRP300HDACLPSSiE - SIESTAT - آمارAngiotensinogen - آنژیوتانسینوژنApr - آوریلsodium dodecyl sulfate–polyacrylamide gel electrophoresis - الکتروفورز ژل دوده سولفات سدیم پلی آکریل آمیدSDS-PAGE - الکتروفورز ژل پلی آکریل آمیدchromatin immunoprecipitation - ایمن سازی کروماتینinterleukin - اینترلوکینTyr - تیرTyrosine - تیروزینnuclear export signal - سیگنال صادرات هسته ایnuclear extract - عصاره هسته ایlipopolysaccharide - لیپوپلی ساکاریدSignal transducer and activator of transcription - مبدل سیگنال و فعال کننده رونویسیwild-type - نوع وحشیAGT - هشتHistone acetyltransferase - هیستون استیل ترانسفرازhistone deacetylase - هیستون داستیلازpolymerase chain reaction - واکنش زنجیره ای پلیمرازPCR - واکنش زنجیرهٔ پلیمرازAntibody - پادتَن یا آنتیبادیCHiP - چیپHAT - کلاه
موضوعات مرتبط
علوم پزشکی و سلامت
پزشکی و دندانپزشکی
بیماریهای گوارشی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Background & Aims: The signal transducers and activators of transcription (STATs) are cytoplasmic transcription factors mediating acute-phase response (APR) of the human angiotensinogen (hAGT) gene in hepatocytes. The mechanisms of how STAT3 activates target genes are unknown. Here we analyzed the biochemistry of STAT3 activation by interleukin (IL)-6 in hepatocellular carcinoma HepG2 and Balb/C mice. Methods: Immunoprecipitation-Western assays and Matrix Assisted Laser Desorption-Time of Flight mass spectrometry determined sites of STAT3 acetylation by the 300-kilodalton target of E1A (p300) co-activator. The subcellular localization of acetylation-deficient STAT3 molecules were studied by microscopic imaging, effects on DNA binding measured by gel shift and chromatin immunoprecipitation (ChIP) assays, and gene transactivation by Northern blot and reporter assays. Results: Two Lys residues at amino acids 49 and 87 in the STAT3 NH2 terminus are acetylated by p300. Lys-to-Arg point mutations (STAT3 K49R/K87R) had no effect on inducible DNA binding, but blocked p300-mediated acetyl(Ac)-STAT3 formation and abrogated IL-6-induced hAGT activation. Although STAT3 K49R/K87R rapidly translocated into the nucleus, it did not bind p300 and had delayed cytoplasmic redistribution. ChIP assays show IL-6-inducible acetylated STAT3 and p300 binding to the native hAGT promoter. Activation of the APR in mice induces nuclear Tyr phosphorylated and acetylated STAT3 in hepatic nuclei. We also observed that STAT3 interacts with histone deacetylases (HDACs), specifically HDAC 1, that down-regulate IL-6-induced hAGT transactivation. Conclusions: IL-6-induced target gene activation requires p300-mediated STAT3 acetylation, and HDACs are involved in the termination of STAT3 action. These studies indicate the acetylation-deacetylation reaction as a novel signaling mechanism controlling the IL-6-STAT3 pathway in the hepatic APR.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Gastroenterology - Volume 129, Issue 5, November 2005, Pages 1616-1632
Journal: Gastroenterology - Volume 129, Issue 5, November 2005, Pages 1616-1632
نویسندگان
Sutapa Ray, Istvan Boldogh, Allan R. Brasier,