Roles of old players in the suppression of a new player: networks for the transcriptional control of angiogenesis.

During the formation of blood vessels, Id1, a member of the helix-loop-helix (HLH) family, and TAL1/SCL, a basic HLH (bHLH) transcription factor, play important roles in the activation of endothelial cells. Recent reports revealed that E2-2, another bHLH transcription factor, inhibits angiogenesis in vitro and in vivo by suppressing the expression of vascular endothelial growth factor receptor 2 (VEGFR2). Id1 and TAL1/SCL dimerize with E2-2 and relieve the E2-2-mediated down-regulation of VEGFR2 expression, leading to the activation of endothelial cells. These findings reveal a novel interplay between HLH transcription factors that regulate angiogenesis.