Endoglin inhibits ERK-induced c-Myc and cyclin D1 expression to impede endothelial cell proliferation

Christopher C. Pan, Jeffrey C. Bloodworth, Karthikeyan Mythreye, Nam Y. Lee

Research output: Contribution to journalArticlepeer-review

23 Scopus citations


Endoglin is an endothelial-specific transforming growth factor beta (TGF-β) co-receptor essential for angiogenesis and vascular remodeling. Endoglin regulates a wide range of cellular processes, including cell adhesion, migration, and proliferation, through TGF-β signaling to canonical Smad and Smad-independent pathways. Despite its overall pro-angiogenic role in the vasculature, the underlying mechanism of endoglin action is poorly characterized. We previously identified β-arrestin2 as a binding partner that causes endoglin internalization from the plasma membrane and inhibits ERK signaling towards endothelial migration. In the present study, we examined the mechanistic role of endoglin and β-arrestin2 in endothelial cell proliferation. We show that endoglin impedes cell growth through sustained inhibition of ERK-induced c-Myc and cyclin D1 expression in a TGF-β-independent manner. The down-regulation of c-Myc and cyclin D1, along with growth-inhibition, are reversed when the endoglin/β-arrestin2 interaction is disrupted. Given that TGF-β-induced Smad signaling potently represses c-Myc in most cell types, our findings here show a novel mechanism by which endoglin augments growth-inhibition by targeting ERK and key downstream mitogenic substrates.

Original languageEnglish (US)
Pages (from-to)620-623
Number of pages4
JournalBiochemical and Biophysical Research Communications
Issue number3
StatePublished - Aug 3 2012


  • C-Myc
  • ERK
  • Endoglin
  • Smads
  • TGF-β
  • β-arrestin2

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology


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