Table 2.
Molecular structure of the t(8;21) fusion protein, the origin of various domains, and the localization of important molecular interactions.
| Origin | Domain (alternative nomenclature) | Molecular interactions |
|---|---|---|
| N-terminal | ||
| AML1 | Runt | DNA binding |
| Binding to CBFβ with formation of heterodimers | ||
| Binding of other transcriptional regulators | ||
| RUNX1T1-derived domains | NHR1 (eTAFH) | Interacts with the nuclear hormone receptor corepressor |
| Interaction with the activation domain of E-proteins (E2A and HEB) | ||
| NHR2 (HHR) | Mediates oligomerization with itself or other ETO molecules | |
| Interacts with the corepressors Sin3, Gfi1, and histone deacetylases 1 and 3 | ||
| NHR3 (Nervy) | Interacts with the regulatory subunit of type II cAMP-dependent protein kinase | |
| This domain together with the NHR4 domain is absent in the leukemogenic AE9a splice variant that naturally occurs in primary human AML cells with t(8;21) | ||
| NHR4 (MYND) | N-CoR and the silencing mediator of retinoid and thyroid hormone receptor (SMRT); these are associated with HDACs | |
| SON, an RNA/DNA-binding protein | ||
| This domain is absent in the leukemogenic AE9a splice variant | ||
| C-Terminal | ||