The ACE2 (angiotensin-converting enzyme 2)/Ang-(1–7) [angiotensin-(1–7)]/MAS axis of the RAS (renin–angiotensin system) has emerged as a pathway of interest in treating both cardiovascular disorders and cancer. The MAS protein is known to bind to and be activated by Ang-(1–7); however, the mechanisms of this activation are just starting to be understood. Although there are strong biochemical data regarding the regulation and activation of the AT1R (angiotensin II type 1 receptor) and the AT2R (angiotensin II type 2 receptor), with models of how AngII (angiotensin II) binds each receptor, fewer studies have characterized MAS. In the present study, we characterize the MAS promoter and provide a potential feedback mechanism that could compensate for MAS degradation following activation by Ang-(1–7). Analysis of ENCODE data for the MAS promoter revealed potential epigenetic control by KRAB (Krüppel-associated box)/KAP-1 (KRAB-associated protein-1). A proximal promoter construct for the MAS gene was repressed by the SOX [SRY (sex-determining region on the Y chromosome) box] proteins SRY, SOX2, SOX3 and SOX14, of which SRY is known to interact with the KRAB domain. The KRAB–KAP-1 complex can be tyrosine-nitrated, causing the dissociation of the KAP-1 protein and thus a potential loss of epigenetic control. Activation of MAS can lead to an increase in nitric oxide, suggesting a feedback mechanism for MAS on its own promoter. The results of the present study provide a more complete view of MAS regulation and, for the first time, suggest biochemical outcomes for nitration of the KRAB domain.
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February 03 2014
MAS promoter regulation: a role for Sry and tyrosine nitration of the KRAB domain of ZNF274 as a feedback mechanism
Jeremy W. Prokop;
Jeremy W. Prokop
*Department of Biology, Program in Integrated Bioscience, The University of Akron, Akron, OH 44325, U.S.A.
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Frank J. Rauscher, III;
Frank J. Rauscher, III
†The Wistar Institute, Philadelphia, PA 19104, U.S.A.
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Hongzhuang Peng;
Hongzhuang Peng
†The Wistar Institute, Philadelphia, PA 19104, U.S.A.
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Yuanjie Liu;
Yuanjie Liu
†The Wistar Institute, Philadelphia, PA 19104, U.S.A.
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Fabiano C. Araujo;
Fabiano C. Araujo
‡National Institute of Science and Technology in Molecular Medicine and Department of Obstetrics and Gynecology, Faculty of Medicine, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil
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Ingrid Watanabe;
Ingrid Watanabe
§Nephrology Division, Department of Medicine, Federal University of Sao Paulo, Sao Paulo, SP, Brazil
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Fernando M. Reis;
Fernando M. Reis
‡National Institute of Science and Technology in Molecular Medicine and Department of Obstetrics and Gynecology, Faculty of Medicine, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil
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Amy Milsted
*Department of Biology, Program in Integrated Bioscience, The University of Akron, Akron, OH 44325, U.S.A.
Correspondence: Professor Amy Milsted (email [email protected]).
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Publisher: Portland Press Ltd
Received:
July 15 2013
Revision Received:
September 23 2013
Accepted:
October 15 2013
Accepted Manuscript online:
October 15 2013
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© The Authors Journal compilation © 2014 Biochemical Society
2014
Clin Sci (Lond) (2014) 126 (10): 727–738.
Article history
Received:
July 15 2013
Revision Received:
September 23 2013
Accepted:
October 15 2013
Accepted Manuscript online:
October 15 2013
Citation
Jeremy W. Prokop, Frank J. Rauscher, Hongzhuang Peng, Yuanjie Liu, Fabiano C. Araujo, Ingrid Watanabe, Fernando M. Reis, Amy Milsted; MAS promoter regulation: a role for Sry and tyrosine nitration of the KRAB domain of ZNF274 as a feedback mechanism. Clin Sci (Lond) 1 May 2014; 126 (10): 727–738. doi: https://doi.org/10.1042/CS20130385
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