Decorin-inducible Peg3 Evokes Beclin 1-mediated Autophagy and Thrombospondin 1-mediated Angiostasis

J Biol Chem. 2017 Mar 24;292(12):5055-5069. doi: 10.1074/jbc.M116.753632. Epub 2017 Feb 7.


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.

Keywords: Beclin-1 (BECN1); angiogenesis; autophagy; cell biology; cell motility; decorin; proteoglycan.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Autophagy
  • Beclin-1 / genetics*
  • Cell Line
  • Cell Movement
  • Decorin / metabolism*
  • Endothelial Cells / cytology
  • Endothelial Cells / metabolism
  • Humans
  • Kruppel-Like Transcription Factors / genetics*
  • Kruppel-Like Transcription Factors / metabolism
  • Neovascularization, Physiologic
  • Promoter Regions, Genetic
  • Thrombospondin 1 / metabolism*
  • Transcriptional Activation
  • Up-Regulation*


  • BECN1 protein, human
  • Beclin-1
  • Decorin
  • Kruppel-Like Transcription Factors
  • PEG3 protein, human
  • Thrombospondin 1