Recruitment of the nuclear receptor corepressor N-CoR by the TEL moiety of the childhood leukemia-associated TEL-AML1 oncoprotein.
The t(12;21)(p13;q22) chromosomal translocation is the most frequent illegitimate gene recombination in a pediatric cancer and occurs in approximately 25% of common acute lymphoblastic leukemia (cALL) cases. This rearrangement results in the in frame fusion of the 5'-region of the ETS-related gene, TEL (ETV6), to almost the entire acute myeloid leukemia 1 (AML1) (also called CBFA2 or PEBP2AB1) locus and expression of the TEL-AML1 chimeric protein. Although AML1 stimulates transcription, TEL-AML1 functions as a repressor of some AML1 target genes. In contrast to the wild type AML1 protein, both TEL and TEL-AML1 interact with N-CoR, a component of the nuclear receptor corepressor complex with histone deacetylase activity. The interaction between TEL and N-CoR requires the central region of TEL, which is retained in TEL-AML1, and TEL lacking this domain is impaired in transcriptional repression. Taken together, our results suggest that TEL-AML1 may contribute to leukemogenesis by recruiting N-CoR to AML1 target genes and thus imposing an altered pattern of their expression.
Guidez
F
F
Leukaemia Research Fund Centre at the Institute of Cancer Research, Chester Beatty Laboratories, London, England.
Petrie
K
K
Ford
A M
AM
Lu
H
H
Bennett
C A
CA
MacGregor
A
A
Hannemann
J
J
Ito
Y
Y
Ghysdael
J
J
Greaves
M
M
Wiedemann
L M
LM
Zelent
A
A
D050676:Core Binding Factor Alpha 2 Subunit; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D015870:Gene Expression; D006801:Humans; D007163:Immunosorbent Techniques; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D056971:Nuclear Receptor Co-Repressor 1; D015514:Oncogene Proteins, Fusion / Q000235:genetics / Q000502:physiology*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000378:metabolism; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D011994:Recombinant Proteins; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D014162:Transfection; D000097764:ETS Translocation Variant 6 Protein
D050676:Core Binding Factor Alpha 2 Subunit; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D056971:Nuclear Receptor Co-Repressor 1; D015514:Oncogene Proteins, Fusion; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D011994:Recombinant Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; D000097764:ETS Translocation Variant 6 Protein; C539127:NCOR1 protein, human; C493728:RUNX1 protein, human; C102421:TEL-AML1 fusion protein