A new line of investigation is the pathogenesis of the translocation (8;21) leukemia, responsible for 15% of all acute myeloid leukemia (AML). This translocation fuses a portion of the AML1 gene on chromosome 21 to the ETO gene on chromosome 8, creating a new protein product called AML1/ETO. In current work, the association of ETO with other nuclear proteins that regulate gene expression was studied using the yeast two-hybrid method. One of the clones identified in this manner was found to have significant homology to the murine nuclear receptor co-repressor (N-CoR), a member of a multi-protein complex that represses transcription through the enzymatic modification of histones. Thus, a novel human N-CoR, which binds to the ETO proto-oncoprotein, has been identified. Future studies will clarify the relationship between ETO and N-CoR and their role in leukemogenesis.
| Wood, J D; Nucifora Jr, F C; Duan, K et al. (2000) Atrophin-1, the dentato-rubral and pallido-luysian atrophy gene product, interacts with ETO/MTG8 in the nuclear matrix and represses transcription. J Cell Biol 150:939-48 |
| Li, J; Wang, J; Wang, J et al. (2000) Both corepressor proteins SMRT and N-CoR exist in large protein complexes containing HDAC3. EMBO J 19:4342-50 |
| Stacey, M W; Wang, J; Byrd, R L et al. (1999) Nuclear receptor co-repressor gene localizes to 17p11.2, a frequently deleted band in malignant disorders. Genes Chromosomes Cancer 25:191-3 |
| Redner, R L; Wang, J; Liu, J M (1999) Chromatin remodeling and leukemia: new therapeutic paradigms. Blood 94:417-28 |
| Wang, J; Saunthararajah, Y; Redner, R L et al. (1999) Inhibitors of histone deacetylase relieve ETO-mediated repression and induce differentiation of AML1-ETO leukemia cells. Cancer Res 59:2766-9 |
