The Arf tumor suppressor regulates platelet-derived growth factor receptor β signaling: A new view through the eyes of Arf-/- mice

J. Derek Thornton, Ricardo L A Silva, Amy C. Martin, Stephen X. Skapek

Research output: Contribution to journalReview articlepeer-review

5 Scopus citations

Abstract

Arf is a key mammalian tumor suppressor gene known to be activated in response to aberrant mitogenic signals leading to both p53-dependent and -independent effects. We recently uncovered a new and somewhat unexpected function for mouse Arf as a regulator of mural cell accumulation within an ocular vascular bed destined to regress in the postnatal period. We found that the Arf gene product, p19Arf, blocks mural cell proliferation driven by Platelet-derived growth factor receptor β (Pdgfrβ) in the developing vitreous. In vivo studies and analyses of cultured cells indicate that p19Arf dampens the expression of Pdgfrβ. In cultured mouse embryo fibroblasts, p19Arf accomplishes this independently of two established effectors - Mdm2 and p53. Our findings indicating that p19 Arf responds to specific developmental cues to disrupt Pdgfrβ signaling in the developing eye extend existing paradigms for Arf tumor suppressor gene biology.

Original languageEnglish (US)
Pages (from-to)1316-1319
Number of pages4
JournalCell Cycle
Volume4
Issue number10
DOIs
StatePublished - Oct 2005

Keywords

  • Arf
  • Persistent hyperplastic primary vitreous
  • Platelet-derived growth factor receptor β
  • Vascular mural cells
  • Vascular regression

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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