A novel E1A-like inhibitor of differentiation (EID) family member, EID-2, suppresses transforming growth factor (TGF)-beta signaling by blocking TGF-beta-induced formation of Smad3-Smad4 complexes.
Smad proteins play key roles in intracellular signaling of the transforming growth factor-beta (TGF-beta) superfamily. E1A, an adenoviral oncoprotein, is known to inhibit TGF-beta-induced transactivation through binding to Smad proteins. Recently, an EID-1 (E1A-like inhibitor of differentiation-1) and EID-2 (EID-1-like inhibitor of differentiation-2) were identified. In this study, we examined the effect of EID-2 on Smad-mediated TGF-beta signaling. Here, we show that EID-2 inhibits TGF-beta/Smad transcriptional responses. EID-2 interacts constitutively with Smad proteins, and most strongly with Smad3. Stable expression of EID-2 in the TGF-beta1-responsive cell line inhibits endogenous Smad3-Smad4 complex formation and TGF-beta1-induced expression of p21 and p15. These results suggest that EID-2 may function as an endogenous suppressor of TGF-beta signaling.
Lee
Ho-Jae
HJ
Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, Bethesda, Maryland 20892-5055, USA.
Lee
Jin Kyung
JK
Miyake
Satoshi
S
Kim
Seong-Jin
SJ
D000818:Animals; D019556:COS Cells; D002352:Carrier Proteins / Q000378:metabolism*; D002522:Chlorocebus aethiops; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006801:Humans; D051797:Inhibitor of Differentiation Protein 2; D047908:Intracellular Signaling Peptides and Proteins; D011485:Protein Binding; D015398:Signal Transduction; D051900:Smad3 Protein; D051901:Smad4 Protein; D015534:Trans-Activators / Q000378:metabolism*; D015533:Transcriptional Activation; D016212:Transforming Growth Factor beta / Q000378:metabolism*
D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C475090:EID2 protein, human; D051797:Inhibitor of Differentiation Protein 2; D047908:Intracellular Signaling Peptides and Proteins; C497790:SMAD3 protein, human; C497796:SMAD4 protein, human; D051900:Smad3 Protein; D051901:Smad4 Protein; D015534:Trans-Activators; D016212:Transforming Growth Factor beta