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  • Original Article
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Members of the hSWI/SNF chromatin remodeling complex associate with and are phosphorylated by protein kinase B/Akt

Abstract

In an adenosine triphosphate (ATP)-dependent process, the hSWI/SNF chromatin remodeling complex functions to alter chromatin structure, thereby regulating transcription factor access to DNA. In addition to interactions with transcription factors and recognition of acetylated histone residues, the chromatin remodeling activity of hSWI/SNF has also been shown to respond to a variety of cell signaling pathways. Our results demonstrate a novel interaction between the serine/threonine kinase Akt and members of the hSWI/SNF chromatin remodeling complex. Activation of Akt in HeLa cells resulted in its association with hSWI/SNF subunits: INI1, BAF155 and BAF170, as well as actin. BAF155 became preferentially recognized by an antibody that detects phosphorylated Akt substrates upon activation of Akt, suggesting that BAF155 may be an in vivo target for phosphorylation by Akt. Glutathione-S-transferase (GST) pulldown experiments demonstrated that INI1 and BAF155 were both capable of directly interacting with Akt. Finally, in vitro kinase assays provided additional evidence that BAF155 and potentially INI1 are substrates for Akt phosphorylation. These data provide the first evidence that Akt signaling may modulate function of the hSWI/SNF complex.

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Accession codes

Accessions

GenBank/EMBL/DDBJ

Abbreviations

hSWI/SNF:

hSWI (switch)/SNF (sucrose non-fermenting)

BRG1/hBrm:

Brahma-related gene 1/human Brahma

BAF:

BRG1-associated factor

INI1:

integrase interactor 1

SMARCB1:

SWI/SNF-related matrix-associated actin-dependent regulator of chromatin B1

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Acknowledgements

We thank Drs Yusuf Hannun (MUSC) and Dennis Watson (MUSC) for critical review of this manuscript and Drs David Kurtz (MUSC), Robin Muise-Helmericks (MUSC), Dennis Watson and Daohong Zhou (MUSC) for helpful discussions and ideas. We additionally thank Dr Robin Muise-Helmericks for reagents and assistance with techniques, as well as Dr William Schubach (University of Washington) for the anti-INI1 antibody, and Dr Timothy Triche (Los Angeles Children's Hospital) for cell lines. Funding for this work was provided by the MUSC Department of Pathology and Laboratory Medicine (CFW, KSJF), Department of Defense grant #N00014-96-1298 (CFW, KSJF), a Hollings Cancer Center Abney Foundation Scholarship (KSJF), and National Institutes of Health grants #T32 DK007431-21 (WJM) and #T35 HL007769-14 (JSR). We also thank the MUSC Nucleic Acids Analysis and Molecular Biology Core Facilities.

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Correspondence to C F Wright.

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Foster, K., McCrary, W., Ross, J. et al. Members of the hSWI/SNF chromatin remodeling complex associate with and are phosphorylated by protein kinase B/Akt. Oncogene 25, 4605–4612 (2006). https://doi.org/10.1038/sj.onc.1209496

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