Identifiers
NAME:E-protein*:ID*
Maps_Modules
HMC:ACTIVATING_INVASION_AND_METASTASIS
EMT Senescence / EMT_REGULATORS
References
PMID:15121845
PMID:18832382
PMID:15181457
ID proteins can form complexes with TCF3 (E47), and inhibit the process of EMT.
PMID:19240756
human E-proteins: E47 (TCF3) and E12 (TCF3) from E2A gene, HEB (TCF12) and E2-2 (TCF4)
ID proteins: (ID1, 2, 3, 4), bind all E-proteins
ID2 binds to APC/C and CDH1
PMID:21041997
A complex formed by Smad3, Smad4 and ATF3 binds sequences in the ID1 promoter and represses its transcription.
The decrease in expression of ID factors then increases activity of E proteins and Twist, resulting in transcriptional repression of the E-Cadherin gene.
The transcription factor HMGA2, whose expression increases during TGFB-induced EMT through a Smad3/4-deoendent mechanism, enhances the expression of SNAIL and TWIST and represses the expression of ID2.
PMID:17615296
Through constitutive association with bHLH E12/E47 proteins, Id proteins maintain epithelial phenotypes by repressing the function of E12/E47, which acts as a repressor of E-cadherin.
Down-regulation of ID1 by Smad2/3/ATF3 complex and of ID2 by TGFB thus relieve this inhibition, permitting conversion of epithelial cells to cells with mesenchymal phenotypes