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Structural Basis for Recognition of SMRT/N-CoR by the MYND Domain and Its Contribution to AML1/ETO's Activity
- Source :
- Cancer Cell. 11:483-497
- Publication Year :
- 2007
- Publisher :
- Elsevier BV, 2007.
-
Abstract
- SummaryAML1/ETO results from the t(8;21) associated with 12%–15% of acute myeloid leukemia. The AML1/ETO MYND domain mediates interactions with the corepressors SMRT and N-CoR and contributes to AML1/ETO's ability to repress proliferation and differentiation of primary bone marrow cells as well as to enhance their self renewal in vitro. We solved the solution structure of the MYND domain and show it to be structurally homologous to the PHD and RING finger families of proteins. We also determined the solution structure of an MYND-SMRT peptide complex. We demonstrated that a single amino acid substitution that disrupts the interaction between the MYND domain and the SMRT peptide attenuated AML1/ETO's effects on proliferation, differentiation, and gene expression.
- Subjects :
- Models, Molecular
Cancer Research
Oncogene Proteins, Fusion
PROTEINS
Cellular differentiation
Gene Expression
Repressor
Bone Marrow Cells
CELLCYCLE
Plasma protein binding
Biology
medicine.disease_cause
Article
Cell Line
Mice
03 medical and health sciences
RUNX1 Translocation Partner 1 Protein
0302 clinical medicine
Protein structure
hemic and lymphatic diseases
medicine
Ring finger
Animals
Humans
Nuclear Receptor Co-Repressor 1
neoplasms
Nuclear receptor co-repressor 1
Cell Proliferation
030304 developmental biology
0303 health sciences
Mutation
Nuclear Proteins
Cell Differentiation
Cell Biology
Molecular biology
Protein Structure, Tertiary
3. Good health
Repressor Proteins
medicine.anatomical_structure
Oncology
030220 oncology & carcinogenesis
Core Binding Factor Alpha 2 Subunit
Protein Binding
Subjects
Details
- ISSN :
- 15356108
- Volume :
- 11
- Database :
- OpenAIRE
- Journal :
- Cancer Cell
- Accession number :
- edsair.doi.dedup.....a4412422b42deca6c1deb6e03a650327