Over expression of wild type or a catalytically dead mutant of Sirtuin 6 does not influence NFκB responses.
SIRT6 is involved in inflammation, aging and metabolism potentially by modulating the functions of both NFκB and HIF1α. Since it is possible to make small molecule activators and inhibitors of Sirtuins we wished to establish biochemical and cellular assays both to assist in drug discovery efforts an...
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2012
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oai:doaj.org-article:554910ddac3e4c48ab605416698c2ab92021-11-18T07:13:16ZOver expression of wild type or a catalytically dead mutant of Sirtuin 6 does not influence NFκB responses.1932-620310.1371/journal.pone.0039847https://doaj.org/article/554910ddac3e4c48ab605416698c2ab92012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22792191/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203SIRT6 is involved in inflammation, aging and metabolism potentially by modulating the functions of both NFκB and HIF1α. Since it is possible to make small molecule activators and inhibitors of Sirtuins we wished to establish biochemical and cellular assays both to assist in drug discovery efforts and to validate whether SIRT6 represents a valid drug target for these indications. We confirmed in cellular assays that SIRT6 can deacetylate acetylated-histone H3 lysine 9 (H3K9Ac), however this deacetylase activity is unusually low in biochemical assays. In an effort to develop alternative assay formats we observed that SIRT6 overexpression had no influence on TNFα induced nuclear translocation of NFκB, nor did it have an effect on nuclear mobility of RelA/p65. In an effort to identify a gene expression profile that could be used to identify a SIRT6 readout we conducted genome-wide expression studies. We observed that overexpression of SIRT6 had little influence on NFκB-dependent genes, but overexpression of the catalytically inactive mutant affected gene expression in developmental pathways.Rachel GrimleyOxana PolyakovaJessica VamathevanJoanne McKenaryBrian HayesChampa PatelJanet SmithAngela BridgesAndrew FosberryAnshu BhardwajaBernadette MouzonChun-Wa ChungNathalie BarrettNicola RichmondSundip ModhaRoberto SolariPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 7, p e39847 (2012) |
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Medicine R Science Q |
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Medicine R Science Q Rachel Grimley Oxana Polyakova Jessica Vamathevan Joanne McKenary Brian Hayes Champa Patel Janet Smith Angela Bridges Andrew Fosberry Anshu Bhardwaja Bernadette Mouzon Chun-Wa Chung Nathalie Barrett Nicola Richmond Sundip Modha Roberto Solari Over expression of wild type or a catalytically dead mutant of Sirtuin 6 does not influence NFκB responses. |
| description |
SIRT6 is involved in inflammation, aging and metabolism potentially by modulating the functions of both NFκB and HIF1α. Since it is possible to make small molecule activators and inhibitors of Sirtuins we wished to establish biochemical and cellular assays both to assist in drug discovery efforts and to validate whether SIRT6 represents a valid drug target for these indications. We confirmed in cellular assays that SIRT6 can deacetylate acetylated-histone H3 lysine 9 (H3K9Ac), however this deacetylase activity is unusually low in biochemical assays. In an effort to develop alternative assay formats we observed that SIRT6 overexpression had no influence on TNFα induced nuclear translocation of NFκB, nor did it have an effect on nuclear mobility of RelA/p65. In an effort to identify a gene expression profile that could be used to identify a SIRT6 readout we conducted genome-wide expression studies. We observed that overexpression of SIRT6 had little influence on NFκB-dependent genes, but overexpression of the catalytically inactive mutant affected gene expression in developmental pathways. |
| format |
article |
| author |
Rachel Grimley Oxana Polyakova Jessica Vamathevan Joanne McKenary Brian Hayes Champa Patel Janet Smith Angela Bridges Andrew Fosberry Anshu Bhardwaja Bernadette Mouzon Chun-Wa Chung Nathalie Barrett Nicola Richmond Sundip Modha Roberto Solari |
| author_facet |
Rachel Grimley Oxana Polyakova Jessica Vamathevan Joanne McKenary Brian Hayes Champa Patel Janet Smith Angela Bridges Andrew Fosberry Anshu Bhardwaja Bernadette Mouzon Chun-Wa Chung Nathalie Barrett Nicola Richmond Sundip Modha Roberto Solari |
| author_sort |
Rachel Grimley |
| title |
Over expression of wild type or a catalytically dead mutant of Sirtuin 6 does not influence NFκB responses. |
| title_short |
Over expression of wild type or a catalytically dead mutant of Sirtuin 6 does not influence NFκB responses. |
| title_full |
Over expression of wild type or a catalytically dead mutant of Sirtuin 6 does not influence NFκB responses. |
| title_fullStr |
Over expression of wild type or a catalytically dead mutant of Sirtuin 6 does not influence NFκB responses. |
| title_full_unstemmed |
Over expression of wild type or a catalytically dead mutant of Sirtuin 6 does not influence NFκB responses. |
| title_sort |
over expression of wild type or a catalytically dead mutant of sirtuin 6 does not influence nfκb responses. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2012 |
| url |
https://doaj.org/article/554910ddac3e4c48ab605416698c2ab9 |
| work_keys_str_mv |
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| _version_ |
1718423786700668928 |