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Recruitment of the nuclear receptor corepressor N-CoR by the TEL moiety of the childhood leukemia-associated TEL-AML1 oncoprotein.

Guidez, Fabien, Petrie, Kevin, Ford, Anthony M, Lu, Huafeng, Bennett, Caroline A, MacGregor, Angus, Hannemann, Jurgen, Ito, Yoshiaki, Ghysdael, Jaques, Greaves, Mel, Wiedemann, Leanne M. and Zelent, Arthur (2000) Recruitment of the nuclear receptor corepressor N-CoR by the TEL moiety of the childhood leukemia-associated TEL-AML1 oncoprotein. Blood, 96 (7). pp. 2557-61. ISSN 0006-4971

Item Type: Article

Abstract

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.

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More Information

Depositing User: Kevin Petrie

Identifiers

Item ID: 12419
Identification Number: https://doi.org/10.1182/blood.V96.7.2557
ISSN: 0006-4971
URI: http://sure.sunderland.ac.uk/id/eprint/12419
Official URL: https://ashpublications.org/blood/article/96/7/255...

Users with ORCIDS

ORCID for Kevin Petrie: ORCID iD orcid.org/0000-0002-9805-9152

Catalogue record

Date Deposited: 18 Aug 2020 09:51
Last Modified: 30 Sep 2020 10:48

Contributors

Author: Kevin Petrie ORCID iD
Author: Fabien Guidez
Author: Anthony M Ford
Author: Huafeng Lu
Author: Caroline A Bennett
Author: Angus MacGregor
Author: Jurgen Hannemann
Author: Yoshiaki Ito
Author: Jaques Ghysdael
Author: Mel Greaves
Author: Leanne M. Wiedemann
Author: Arthur Zelent

University Divisions

Faculty of Health Sciences and Wellbeing > School of Medicine

Subjects

Sciences > Biomedical Sciences
Sciences > Health Sciences

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