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SIRT2 gene has a classic SRE element, is a downstream target of serum response factor and is likely activated during serum stimulation

The sirtuin proteins are an evolutionarily conserved family of NAD(+)-dependent deacetylases that regulate various cellular functions. Among the seven sirtuins, SIRT2 is predominantly found in the cytoplasm, and is present in a wide range of tissues. Recent studies indicate that SIRT2 plays an impor...

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Autores principales: Zhang, Xiaomin, Azhar, Gohar, Wei, Jeanne Y.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5739444/
https://www.ncbi.nlm.nih.gov/pubmed/29267359
http://dx.doi.org/10.1371/journal.pone.0190011
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author Zhang, Xiaomin
Azhar, Gohar
Wei, Jeanne Y.
author_facet Zhang, Xiaomin
Azhar, Gohar
Wei, Jeanne Y.
author_sort Zhang, Xiaomin
collection PubMed
description The sirtuin proteins are an evolutionarily conserved family of NAD(+)-dependent deacetylases that regulate various cellular functions. Among the seven sirtuins, SIRT2 is predominantly found in the cytoplasm, and is present in a wide range of tissues. Recent studies indicate that SIRT2 plays an important role in metabolic homeostasis. Several studies indicate that SIRT2 is upregulated under serum deprivation conditions. Since the serum response factor gene usually responds rapidly to serum deprivation and/or serum restoration following deprivation, we hypothesized that a common mechanism may serve to regulate both SIRT2 and SRF during serum stimulation. Using a bioinformatics approach, we searched the SRF binding motif in the SIRT2 gene, and found one classic CArG element (CCATAATAGG) in the SIRT2 gene promoter, which was bound to SRF in the electrophoretic mobility shift assay (EMSA). Serum deprivation induced SIRT2 expression, while SRF and the SRF binding protein, p49/STRAP, repressed SIRT2 gene expression. SIRT2 gene expression was also repressed by the Rho/SRF inhibitor, CCG-1423. These data demonstrate that the classic SRE element in the SIRT2 gene promoter region is functional and therefore, SIRT2 gene is a downstream target of the Rho/SRF signaling pathway. The increased expression of SRF that was observed in the aged heart may affect SIRT2 gene expression and contribute to altered metabolic status in senescence.
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spelling pubmed-57394442018-01-10 SIRT2 gene has a classic SRE element, is a downstream target of serum response factor and is likely activated during serum stimulation Zhang, Xiaomin Azhar, Gohar Wei, Jeanne Y. PLoS One Research Article The sirtuin proteins are an evolutionarily conserved family of NAD(+)-dependent deacetylases that regulate various cellular functions. Among the seven sirtuins, SIRT2 is predominantly found in the cytoplasm, and is present in a wide range of tissues. Recent studies indicate that SIRT2 plays an important role in metabolic homeostasis. Several studies indicate that SIRT2 is upregulated under serum deprivation conditions. Since the serum response factor gene usually responds rapidly to serum deprivation and/or serum restoration following deprivation, we hypothesized that a common mechanism may serve to regulate both SIRT2 and SRF during serum stimulation. Using a bioinformatics approach, we searched the SRF binding motif in the SIRT2 gene, and found one classic CArG element (CCATAATAGG) in the SIRT2 gene promoter, which was bound to SRF in the electrophoretic mobility shift assay (EMSA). Serum deprivation induced SIRT2 expression, while SRF and the SRF binding protein, p49/STRAP, repressed SIRT2 gene expression. SIRT2 gene expression was also repressed by the Rho/SRF inhibitor, CCG-1423. These data demonstrate that the classic SRE element in the SIRT2 gene promoter region is functional and therefore, SIRT2 gene is a downstream target of the Rho/SRF signaling pathway. The increased expression of SRF that was observed in the aged heart may affect SIRT2 gene expression and contribute to altered metabolic status in senescence. Public Library of Science 2017-12-21 /pmc/articles/PMC5739444/ /pubmed/29267359 http://dx.doi.org/10.1371/journal.pone.0190011 Text en © 2017 Zhang et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Zhang, Xiaomin
Azhar, Gohar
Wei, Jeanne Y.
SIRT2 gene has a classic SRE element, is a downstream target of serum response factor and is likely activated during serum stimulation
title SIRT2 gene has a classic SRE element, is a downstream target of serum response factor and is likely activated during serum stimulation
title_full SIRT2 gene has a classic SRE element, is a downstream target of serum response factor and is likely activated during serum stimulation
title_fullStr SIRT2 gene has a classic SRE element, is a downstream target of serum response factor and is likely activated during serum stimulation
title_full_unstemmed SIRT2 gene has a classic SRE element, is a downstream target of serum response factor and is likely activated during serum stimulation
title_short SIRT2 gene has a classic SRE element, is a downstream target of serum response factor and is likely activated during serum stimulation
title_sort sirt2 gene has a classic sre element, is a downstream target of serum response factor and is likely activated during serum stimulation
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5739444/
https://www.ncbi.nlm.nih.gov/pubmed/29267359
http://dx.doi.org/10.1371/journal.pone.0190011
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