Various proteins interacting with NICD
| Symbol | Protein | Interface with NICD |
|---|---|---|
| Regulation of NICD by phosphorylation | ||
| GSK3β | Glycogen synthase kinase 3 | Phosphorylates Notch, which can lead to degradation or stabilization |
| CycC | Cyclin C | Target NICD along with CDk8 for phosphorylation that subsequently acts as substrate for ubiquitylation and degradation |
| CDK8 | Cyclin-dependent kinase 8 | Phosphorylates NICD with CycC that subsequently acts as substrate for ubiquitylation and degradation |
| G-CSF | Granulocyte colony-stimulating factor | Phosphorylation of NICD that subsequently leads to its inactivation |
| Regulation of NICD by ubiquitylation | ||
| Fbxw7/Cdc4 | F-box/WD-repeat protein 7 | Ubiquitylates the NICD leading to its degradation |
| Numb | Numb homolog | Suppresses Notch signaling by recruiting E3 ubiquitin ligases to ubiquitylate Notch |
| Dtx1–4 | Deltex 1–4 | Controls Notch ubiquitylation, processing, and internalization |
| Itch | Itchy, E3 ubiquitin protein ligase | Promotes ubiquitylation of NICD |
| Regulation of NICD by hydroxylation | ||
| FIH | Factor inhibiting HIF1α | Hydroxylates the Notch and represses Notch |
| HIF1α | Hypoxia-inducible factor 1, alpha subunit | Stabilizes the NICD and synergizes with it in transcription of Notch target genes |
| Miscellaneous proteins interacting with NICD | ||
| Axin | Axin | Synergies with NICD to regulate the stability of β-catenin and controls the trafficking of NICD in association with adenomatous polyposis coli |
| Apc | Adenomatous polyposis coli | Control the trafficking of Notch |
| CSL/RBP-jκ | CBF1, Su(H) and LAG-1/RBP-jκ | Key canonical transcriptional cofactor for NICD |
| Ctnnb1 | β-catenin | Synergies with NICD/CSL on Notch target gene |
| Dab | Disabeled | Acts as link to Abelson tyrosine kinase (Abl) protein in noncanonical Notch axon guidance |
| Dvl/Dsh | Dishevelled | Dishevelled regulates ligand-dependent Notch trafficking and inhibits canonical Notch signaling |
| MAML-1/2 | Master mind-like-1/2 | Coactivator of NICD/CSL |
| NF-κB | Nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 | NICD blocks NF-κB transcription of NF-κB target genes through binding to p50/cRel |
| Nrarp | Notch-regulated ankyrin repeat protein | Nrarp binds and inhibits the NICD/CSL |
| p73α (TA) | Tumor protein p73 alpha (transactivating form) | Binds NICD and inhibits the NICD/CSL-mediated transcription |
| RITA/C12ORF52 | RBP-jκ interacting and tubulin associated | Shuttles NICD between the nucleus and cytoplasm on tubulin networks |
| SMAD | Smad family members | Smads augment Notch signaling, Notch fine-tunes signaling via Smads |
| SNW1/SKIP/NCOA-62 | SNW domain-containing protein 1/Ski-interacting protein/Nuclear receptor coactivator NCoA-62 | Can bind both NICD and corepressor SMRT, but these are mutually exclusive; forms multimers with NICD and MAML, which then associates with CSL to activate transcription |
| Tacc3 | Transforming, acidic coiled-coil containing protein 3 | Binds NICD and blocks transcription from Notch target promoters; can be reversed by overexpression of CSL |
| Trio | Triple functional domain (PTPRF interacting) | A guanine nucleotide exchange factor (GEF) for Rho GTPases that acts as link to Abelson tyrosine kinase (Abl) proteins in noncanonical Notch axon guidance |
CDK, cyclin-dependent kinase; E3, ubiquitin ligase; HIF, hypoxia-inducible factor; NF-κB, nuclear factor kappa-light-chain-enhancer of activated B cells; RITA, RBP-jκ interacting and tubulin–associated; SKIP, Ski-interacting protein; SMRT, a silencing mediator for retinoid or thyroid hormone receptors.