Ets family members share a conserved DNA-binding ETS domain, and serve a variety of roles in development, differentiation and oncogenesis. Besides DNA binding, the ETS domain also participates in protein–protein interactions with other structurally unrelated transcription factors. Although this mechanism appears to confer tissue- or development stage-specific functions on individual Ets proteins, the biological significance of many of these interactions remains to be evaluated, because their molecular basis has been elusive. We previously demonstrated a direct interaction between the ETS domain of the widely expressed GABPα (GA-binding protein α) and the granulocyte inducer C/EBPα (CCAAT/enhancer-binding protein α), and suggested its involvement in co-operative transcriptional activation of myeloid-specific genes, such as human FCAR encoding FcαR [Fc receptor for IgA (CD89)]. By deletion analysis, we identified helix α3 and the β3/β4 region as the C/EBPα-interacting region. Domain-swapping of individual sub-domains with those of other Ets proteins allowed us to highlight β-strand 3 and the subsequent loop, which when exchanged by those of Elf-1 (E74-like factor 1) reduced the ability to recruit C/EBPα. Further analysis identified a four-amino acid swap mutation of this region (I387L/C388A/K393Q/F395L) that reduces both physical interaction and co-operative transcriptional activation with C/EBPα without affecting its transactivation capacity by itself. Moreover, re-ChIP (re-chromatin immunoprecipitation) analysis demonstrated that GABPα recruits C/EBPα to the FCAR promoter, depending on these residues. The identified amino acid residues could confer the specificity of the action on the Ets proteins in diverse biological processes through mediating the recruitment of its partner factor.
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Research Article|
July 28 2010
Amino acid residues in the β3 strand and subsequent loop of the conserved ETS domain that mediate basic leucine zipper (bZIP) recruitment and potentially distinguish functional attributes of Ets proteins
Toshibumi Shimokawa;
Toshibumi Shimokawa
1Division of Molecular Cell Immunology and Allergology, Nihon University Graduate School of Medical Science, Itabashi-ku, Tokyo 173-8610, Japan
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Satoshi Nunomura;
Satoshi Nunomura
1Division of Molecular Cell Immunology and Allergology, Nihon University Graduate School of Medical Science, Itabashi-ku, Tokyo 173-8610, Japan
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Yukinori Enomoto;
Yukinori Enomoto
1Division of Molecular Cell Immunology and Allergology, Nihon University Graduate School of Medical Science, Itabashi-ku, Tokyo 173-8610, Japan
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Chisei Ra
Chisei Ra
1
1Division of Molecular Cell Immunology and Allergology, Nihon University Graduate School of Medical Science, Itabashi-ku, Tokyo 173-8610, Japan
1To whom correspondence should be addressed (email fcericra@med.nihon-u.ac.jp).
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Publisher: Portland Press Ltd
Received:
November 27 2009
Revision Received:
May 25 2010
Accepted:
June 03 2010
Accepted Manuscript online:
June 03 2010
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2010 Biochemical Society
2010
Biochem J (2010) 430 (1): 129–139.
Article history
Received:
November 27 2009
Revision Received:
May 25 2010
Accepted:
June 03 2010
Accepted Manuscript online:
June 03 2010
Citation
Toshibumi Shimokawa, Satoshi Nunomura, Yukinori Enomoto, Chisei Ra; Amino acid residues in the β3 strand and subsequent loop of the conserved ETS domain that mediate basic leucine zipper (bZIP) recruitment and potentially distinguish functional attributes of Ets proteins. Biochem J 15 August 2010; 430 (1): 129–139. doi: https://doi.org/10.1042/BJ20091742
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