MAS promoter regulation : a role for Sry and tyrosine nitration of the KRAB domain of ZNF274 as a feedback mechanism
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2014 |
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| Erschienen: |
2014 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:126 |
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| Enthalten in: |
Clinical science (London, England : 1979) - 126(2014), 10 vom: 18. Mai, Seite 727-38 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Prokop, Jeremy W [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 02.04.2014 Date Revised 03.12.2021 published: Print Citation Status MEDLINE |
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| doi: |
10.1042/CS20130385 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM231725159 |
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| 100 | 1 | |a Prokop, Jeremy W |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a MAS promoter regulation |b a role for Sry and tyrosine nitration of the KRAB domain of ZNF274 as a feedback mechanism |
| 264 | 1 | |c 2014 | |
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| 500 | |a Date Completed 02.04.2014 | ||
| 500 | |a Date Revised 03.12.2021 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Kruppel-Like Transcription Factors |2 NLM | |
| 650 | 7 | |a Proto-Oncogene Mas |2 NLM | |
| 650 | 7 | |a Proto-Oncogene Proteins |2 NLM | |
| 650 | 7 | |a Receptors, G-Protein-Coupled |2 NLM | |
| 650 | 7 | |a SRY protein, human |2 NLM | |
| 650 | 7 | |a Sex-Determining Region Y Protein |2 NLM | |
| 650 | 7 | |a ZNF274 protein, human |2 NLM | |
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| 650 | 7 | |a Tyrosine |2 NLM | |
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| 700 | 1 | |a Rauscher, Frank J |c 3rd |e verfasserin |4 aut | |
| 700 | 1 | |a Peng, Hongzhuang |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Yuanjie |e verfasserin |4 aut | |
| 700 | 1 | |a Araujo, Fabiano C |e verfasserin |4 aut | |
| 700 | 1 | |a Watanabe, Ingrid |e verfasserin |4 aut | |
| 700 | 1 | |a Reis, Fernando M |e verfasserin |4 aut | |
| 700 | 1 | |a Milsted, Amy |e verfasserin |4 aut | |
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