Based on studies in mice, NOTCH3 intracellular domain NICD3 ...
| created | [InstanceEdit:9016906] Orlic-Milacic, Marija, 2017-08-16 |
| dbId | 9016905 |
| displayName | Based on studies in mice, NOTCH3 intracellular domain NICD3 ... |
| literatureReference |
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| modified | [InstanceEdit:9017731] Orlic-Milacic, Marija, 2017-08-24 |
| schemaClass | Summation |
| text | Based on studies in mice, NOTCH3 intracellular domain NICD3 positively regulates transcription of the PTCRA gene, encoding pre-T-cell receptor alpha (pre-TCR-alpha or pTalpha). NICD3-mediated induction of PTCRA transcription is RBPJ and MAML dependent, and the PTCRA promoter contains several RBPJ-binding sites (Talora et al. 2003, Bellavia et al. 2007). IK1, splicing isoform of the transcription factor Ikaros (IKZF1), competes with RBPJ for binding to the PTCRA promoter and inhibits PTCRA transcription. NOTCH3, through pre-TCR signaling, stimulates expression of the RNA binding protein HuD, which promotes splicing of IKZF1 into dominant negative isoforms. These dominant negative isoforms of IKZF1 heterodimerize with IK1, preventing its binding to target DNA sequences and thus contributing to sustained transcription of PTCRA (Bellavia et al. 2007, reviewed by Bellavia, Mecarrozzi, Campese, Grazioli, Gulino and Screpanti 2007). |
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