Preparing your results

Our searching services are busy right now. Your search will reload in five seconds.

X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

Notch4 intracellular domain binding to Smad3 and inhibition of the TGF-beta signaling.

Oncogene | Aug 11, 2005

http://www.ncbi.nlm.nih.gov/pubmed/16007227

We present evidence that Notch4ICD attenuates TGF-beta signaling. Cells expressing the activated form of the Notch4 receptor (ICD4) were resistant to the growth-inhibitory effects of TGF-beta. Notch4ICD was found to bind to Smad2, Smad3 and Smad4 but with higher affinity to Smad3. Deletion analysis showed that binding of Smad3 to ICD4 was mediated by its MH2 domain and was not dependent on the presence of the RAM23 region in ICD4. Using two TGF-beta/Activin reporter luciferase assays, RT-PCR and Western blot analysis, we demonstrate that ICD4 and ICD4 deltaRAM23 inhibit Smad-binding element and 3TP luciferase reporter activity and PAI-1 gene expression. MCF-7 human breast cancer cells express Notch4ICD (ICD4) and are resistant to the growth-inhibitory effects of TGF-beta. Blockage of Notch4 processing to ICD4 by gamma-secretase inhibitor renders MCF-7 cells sensitive to growth inhibition by TGF-beta. The interplay between these two signaling pathways may be a significant determinant during mammary tumorigenesis.

Pubmed ID: 16007227 RIS Download

Mesh terms: Amino Acid Motifs | Animals | Blotting, Western | Breast Neoplasms | DNA-Binding Proteins | Female | Humans | Mice | Polymerase Chain Reaction | Protein Structure, Tertiary | Proto-Oncogene Proteins | Receptors, Cell Surface | Receptors, Notch | Signal Transduction | Smad3 Protein | Trans-Activators | Transforming Growth Factor beta | Tumor Cells, Cultured

Research resources used in this publication

None found

Research tools detected in this publication

None found

Data used in this publication

None found

Associated grants

None

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.