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Regulation of CD40 and CD40 ligand by the AT-hook transcription factor AKNA

Nature volume 410, pages 383–387 (2001)Cite this article

Abstract

Proteins containing AT hooks bind A/T-rich DNA through a nine-amino-acid motif and are thought to co-regulate transcription by modifying the architecture of DNA, thereby enhancing the accessibility of promoters to transcription factors1,2. Here we describe AKNA, a human AT-hook protein that directly binds the A/T-rich regulatory elements of the promoters of CD40 and CD40 ligand (CD40L) and coordinately regulates their expression. Consistent with its function, AKNA is a nuclear protein that contains multiple PEST protein-cleavage motifs, which are common in regulatory proteins with high turnover rates3. AKNA is mainly expressed by B and T lymphocytes, natural killer cells and dendritic cells. During B-lymphocyte differentiation, AKNA is mainly expressed by germinal centre B lymphocytes, a stage in which receptor and ligand interactions are crucial for B-lymphocyte maturation4,5,6,7,8,9,10,11,12. Our findings show that an AT-hook molecule can coordinately regulate the expression of a key receptor and its ligand, and point towards a molecular mechanism that explains homotypic cell interactions.

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Figure 1: AKNA is predominantly expressed by secondary lymphoid organs.
Figure 2: Expression of AKNA by B and T lymphocytes, NKC and CD1a+CD14- cells.
Figure 3: AKNA has an AT-hook motif and multiple PEST domains.
Figure 4: AKNA expression localizes in the nucleus.
Figure 5: Concomitant expression of AKNA, Fas, CD40 and CD40L by germinal centre B lymphocytes.
Figure 6: Upregulation of CD40 and CD40L expression.

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Acknowledgements

We thank H. N. Ananthaswamy, G. B. Mills and M. F. Wilkinson for comments and advice. This work was supported by a grant from the Leukemia and Lymphoma Society. J.C.S. and R.R. were supported by the Smith pre-doctoral fellowship. L.G.-R. and R.R. are graduate students from the Department of Immunology, School of Biological Sciences, at the Autonomous University of Nuevo Leon, Mexico. L.G.-R. is a recipient of a fellowship from the Consejo Nacional de Ciencia y Tecnologia, Mexico.

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Author notes

  1. Aisha Siddiqa, Jennifer C. Sims-Mourtada, Liliana Guzman-Rojas, Roberto Rangel and Vicente Madrid-Marina: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Immunology, Box 178, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, 77030, Texas, USA

    Aisha Siddiqa, Jennifer C. Sims-Mourtada, Liliana Guzman-Rojas, Roberto Rangel, Yan Sun & Hector Martinez-Valdez

  2. Laboratory for Immunology Research, Schering-Plough, 27 Chemin des Peupliers, 69571, Dardilly, Cedex, France

    Christiane Guret

  3. Centro de Investigacion Sobre Enfermedades Infecciosas, Instituto Nacional de Salud Publica, Ave. Universidad 655, Cuernavaca, 62508, Morelos, Mexico

    Vicente Madrid-Marina

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Correspondence to Hector Martinez-Valdez.

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Siddiqa, A., Sims-Mourtada, J., Guzman-Rojas, L. et al. Regulation of CD40 and CD40 ligand by the AT-hook transcription factor AKNA. Nature 410, 383–387 (2001). https://doi.org/10.1038/35066602

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