Novel complex of HAT protein TIP60 and nuclear receptor PXR promotes cell migration and adhesion

Abstract PXR is a member of nuclear receptor superfamily and a well-characterized mediator of xenobiotic metabolism. The classical mode of PXR activation involves its binding to appropriate ligand and subsequent heterodimerization with its partner RXR. However, various factors such as post-translati...

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Autores principales: Karishma Bakshi, B. Ranjitha, Shraddha Dubey, Jaisri Jagannadham, Bharti Jaiswal, Ashish Gupta
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Publicado: Nature Portfolio 2017
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spelling oai:doaj.org-article:7d754198b12f45f2b165e5658feeee642021-12-02T12:32:59ZNovel complex of HAT protein TIP60 and nuclear receptor PXR promotes cell migration and adhesion10.1038/s41598-017-03783-w2045-2322https://doaj.org/article/7d754198b12f45f2b165e5658feeee642017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-03783-whttps://doaj.org/toc/2045-2322Abstract PXR is a member of nuclear receptor superfamily and a well-characterized mediator of xenobiotic metabolism. The classical mode of PXR activation involves its binding to appropriate ligand and subsequent heterodimerization with its partner RXR. However, various factors such as post-translational modifications and crosstalk with different cellular factors may also regulate the functional dynamics and behavior of PXR. In the present study, we have identified that TIP60, an essential lysine acetyltransferase protein interacts with unliganded PXR and together this complex promotes cell migration & adhesion. TIP60 utilizes its NR Box to interact with LBD region of PXR and acetylates PXR at lysine 170 to induce its intranuclear reorganization. Also, RXR is not required for TIP60-PXR complex formation and this complex does not induce ligand-dependent PXR target gene transactivation. Interestingly, we observed that PXR augments the catalytic activity of TIP60 for histones. This is the first report demonstrating the exclusive interaction of TIP60 with PXR and uncovers a potential role for the TIP60-PXR complex in cell migration and adhesion.Karishma BakshiB. RanjithaShraddha DubeyJaisri JagannadhamBharti JaiswalAshish GuptaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-16 (2017)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Karishma Bakshi
B. Ranjitha
Shraddha Dubey
Jaisri Jagannadham
Bharti Jaiswal
Ashish Gupta
Novel complex of HAT protein TIP60 and nuclear receptor PXR promotes cell migration and adhesion
description Abstract PXR is a member of nuclear receptor superfamily and a well-characterized mediator of xenobiotic metabolism. The classical mode of PXR activation involves its binding to appropriate ligand and subsequent heterodimerization with its partner RXR. However, various factors such as post-translational modifications and crosstalk with different cellular factors may also regulate the functional dynamics and behavior of PXR. In the present study, we have identified that TIP60, an essential lysine acetyltransferase protein interacts with unliganded PXR and together this complex promotes cell migration & adhesion. TIP60 utilizes its NR Box to interact with LBD region of PXR and acetylates PXR at lysine 170 to induce its intranuclear reorganization. Also, RXR is not required for TIP60-PXR complex formation and this complex does not induce ligand-dependent PXR target gene transactivation. Interestingly, we observed that PXR augments the catalytic activity of TIP60 for histones. This is the first report demonstrating the exclusive interaction of TIP60 with PXR and uncovers a potential role for the TIP60-PXR complex in cell migration and adhesion.
format article
author Karishma Bakshi
B. Ranjitha
Shraddha Dubey
Jaisri Jagannadham
Bharti Jaiswal
Ashish Gupta
author_facet Karishma Bakshi
B. Ranjitha
Shraddha Dubey
Jaisri Jagannadham
Bharti Jaiswal
Ashish Gupta
author_sort Karishma Bakshi
title Novel complex of HAT protein TIP60 and nuclear receptor PXR promotes cell migration and adhesion
title_short Novel complex of HAT protein TIP60 and nuclear receptor PXR promotes cell migration and adhesion
title_full Novel complex of HAT protein TIP60 and nuclear receptor PXR promotes cell migration and adhesion
title_fullStr Novel complex of HAT protein TIP60 and nuclear receptor PXR promotes cell migration and adhesion
title_full_unstemmed Novel complex of HAT protein TIP60 and nuclear receptor PXR promotes cell migration and adhesion
title_sort novel complex of hat protein tip60 and nuclear receptor pxr promotes cell migration and adhesion
publisher Nature Portfolio
publishDate 2017
url https://doaj.org/article/7d754198b12f45f2b165e5658feeee64
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