Decorin-inducible Peg3 Evokes Beclin 1-mediated Autophagy and Thrombospondin 1-mediated Angiostasis.
J Biol Chem
; 292(12): 5055-5069, 2017 03 24.
Article
en En
| MEDLINE
| ID: mdl-28174297
ABSTRACT
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.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Regulación hacia Arriba
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Trombospondina 1
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Factores de Transcripción de Tipo Kruppel
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Decorina
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Beclina-1
Límite:
Humans
Idioma:
En
Revista:
J Biol Chem
Año:
2017
Tipo del documento:
Article