FOXP3 is a homo-oligomer and a component of a supramolecular regulatory complex disabled in the human XLAAD/IPEX autoimmune disease.

Li, B; Samanta, A; Song, X; Iacono, K; Brennan, P; Chatila, T; Roncador, G; Banham, A; Riley, J; Wang, Q; Shen, Y; Saouaf, S; Greene, M

Journal article

FOXP3 is a homo-oligomer and a component of a supramolecular regulatory complex disabled in the human XLAAD/IPEX autoimmune disease.

Abstract:: We have found that FOXP3 is an oligomeric component of a large supramolecular complex. Certain FOXP3 mutants with single amino acid deletions in the leucine zipper domain of FOXP3 are associated with the X-linked autoimmunity-allergic dysregulation (XLAAD) and immunodysregulation, polyendocrinopathy and enteropathy, X-linked (IPEX) syndrome in humans. We report that the single amino acid deletion found in human XLAAD/IPEX patients within the leucine zipper domain of FOXP3 does not disrupt its ability to join the larger protein complex, but eliminates FOXP3 homo-oligomerization as well as heteromerization with FOXP1. We found that the zinc finger-leucine zipper domain region of FOXP3 is sufficient to mediate both homodimerization and homotetramerization. However, the same domain region from XLAAD/IPEX FOXP3 containing an E251 deletion prevents oligomerizaton and the protein remains monomeric. We also found that wild-type FOXP3 directly binds to the human IL-2 promoter, but the E251 deletion in FOXP3 in XLAAD/IPEX patient's T cells disrupts its association with the IL-2 promoter in vivo and in vitro, and limits repression of IL-2 transcription after T-cell activation. Our results suggest that compromising FOXP3 homo-oligomerization and hetero-oligomerization with the FOXP1 protein impairs DNA-binding properties leading to distinct biochemical phenotypes in humans with the XLAAD/IPEX autoimmune syndrome. This study explains some features of the pathogenesis of a disease syndrome that arises as a consequence of specific assembly failure of a transcriptional repressor due to certain mutations within the FOXP3 leucine zipper.

Publication status:: Published

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APA Style

Li, B., Samanta, A., Song, X., Iacono, K., Brennan, P., Chatila, T., Roncador, G., Banham, A., Riley, J., Wang, Q., Shen, Y., Saouaf, S., & Greene, M. (2007). FOXP3 is a homo-oligomer and a component of a supramolecular regulatory complex disabled in the human XLAAD/IPEX autoimmune disease. International Immunology, 19(7), 825–835.

MLA Style

Li, B, et al. “FOXP3 Is a Homo-Oligomer and a Component of a Supramolecular Regulatory Complex Disabled in the Human XLAAD/IPEX Autoimmune Disease.” International Immunology, vol. 19, no. 7, 2007, pp. 825–35.

Chicago Style

Li, B, A Samanta, X Song, et al. 2007. “FOXP3 Is a Homo-Oligomer and a Component of a Supramolecular Regulatory Complex Disabled in the Human XLAAD/IPEX Autoimmune Disease.” International Immunology 19 (7): 825–35.
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