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10.1074/jbc.M116.753632

http://scihub22266oqcxt.onion/10.1074/jbc.M116.753632
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C5377817!5377817!28174297
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suck abstract from ncbi


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pmid28174297      J+Biol+Chem 2017 ; 292 (12): 5055-69
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  • Decorin-inducible Peg3 Evokes Beclin 1-mediated Autophagy and Thrombospondin 1-mediated Angiostasis* #MMPMID28174297
  • Torres A; Gubbiotti MA; Iozzo RV
  • J Biol Chem 2017[Mar]; 292 (12): 5055-69 PMID28174297show ga
  • We previously discovered that systemic delivery of decorin for treatment of breast carcinoma xenografts induces paternally expressed gene 3 (Peg3), an imprinted gene encoding a zinc finger transcription factor postulated to function as a tumor suppressor. Here we found that de novo expression of Peg3 increased Beclin 1 promoter activity and protein expression. This process required the full-length Peg3 as truncated mutants lacking either the N-terminal SCAN domain or the zinc fingers failed to translocate to the nucleus and promote Beclin 1 transcription. Importantly, overexpression of Peg3 in endothelial cells stimulated autophagy and concurrently inhibited endothelial cell migration and evasion from a 3D matrix. Mechanistically, we found that Peg3 induced the secretion of the powerful angiostatic glycoprotein Thrombospondin 1 independently of Beclin 1 transcriptional induction. Thus, we provide a new mechanism whereby Peg3 can simultaneously evoke autophagy in endothelial cells and attenuate angiogenesis.
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