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All-trans retinoic acid up-regulates the human CD2AP gene expression through Sp1/Sp3 binding sites

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Abstract

All-trans retinoic acid (ATRA), an active metabolite of vitamin A, plays an important role in regulating cell differentiation, proliferation, and apoptosis. It was reported that ATRA could cause an up-regulation of protein expression of CD2AP in nephrotic animals. However, the mechanism of ATRA-mediated up-regulation is not well understood. In the present study, deletion analysis and luciferase assays demonstrated that ATRA caused a marked increase in the activity of the CD2AP promoter, and the region between nt −599 and −328 from the transcription start site, where there are two clusters of Sp1/3 binding sites, was indispensable for ATRA-mediated up-regulation. Chromatin immunoprecipitation assays revealed that ATRA activated the CD2AP transcription through enhancing the DNA-binding activity of Sp1 and Sp3 with the CD2AP promoter. Taken together, this study provided evidence for the first time showing the stimulating effect of ATRA on CD2AP and new therapeutic strategies for the treatment of nephritic syndrome and other associated diseases of CD2AP deficiency.

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Acknowledgments

This work was supported by the National Natural Science Foundation of China [Grant Numbers 30872804 and 81170661 (to G.P.Z.), 81302531 (to H.G.X.)], Natural Science Foundation of Jiangsu Province of China [Grant Number BK20131018 (to H.G.X.)], Specialized Research Fund for the Doctoral Program of Higher Education [Grant Number 20113234110010 (to G.P.Z.)], and the Priority Academic Program Development of Jiangsu Higher Education Institutions.

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The authors declare that they have no conflict of interest.

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This article does not contain any studies with human participants or animals performed by any of the authors. For this type of study formal consent is not required.

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Authors and Affiliations

  1. Department of Pediatrics, The First Affiliated Hospital, Nanjing Medical University, 300 Guang Zhou Road, Nanjing, 210029, Jiangsu Province, China

    Hua-Guo Xu, Rui Jin, Shan Gao, Wei Ren, Li Zou, Lifei Liu & Guo-Ping Zhou

  2. Department of Laboratory Medicine, The First Affiliated Hospital, Nanjing Medical University, Nanjing, 210029, Jiangsu Province, China

    Hua-Guo Xu

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  1. Hua-Guo Xu
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  2. Rui Jin
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  7. Guo-Ping Zhou
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Correspondence to Guo-Ping Zhou.

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Xu, HG., Jin, R., Gao, S. et al. All-trans retinoic acid up-regulates the human CD2AP gene expression through Sp1/Sp3 binding sites. Immunol Res 62, 273–279 (2015). https://doi.org/10.1007/s12026-015-8658-9

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