| First Author | Pan CC | Year | 2012 |
| Journal | Biochem Biophys Res Commun | Volume | 424 |
| Issue | 3 | Pages | 620-3 |
| PubMed ID | 22789855 | Mgi Jnum | J:186232 |
| Mgi Id | MGI:5431245 | Doi | 10.1016/j.bbrc.2012.06.163 |
| Citation | Pan CC, et al. (2012) Endoglin inhibits ERK-induced c-Myc and cyclin D1 expression to impede endothelial cell proliferation. Biochem Biophys Res Commun 424(3):620-3 |
| abstractText | Endoglin is an endothelial-specific transforming growth factor beta (TGF-beta) co-receptor essential for angiogenesis and vascular remodeling. Endoglin regulates a wide range of cellular processes, including cell adhesion, migration, and proliferation, through TGF-beta 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 beta-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 beta-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-beta-independent manner. The down-regulation of c-Myc and cyclin D1, along with growth-inhibition, are reversed when the endoglin/beta-arrestin2 interaction is disrupted. Given that TGF-beta-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. |
