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.

Aurora AIs a Repressed Effector Target of the Chromatin Remodeling Protein INI1/hSNF5 Required for Rhabdoid Tumor Cell Survival

“…We and other groups have shown that INI1/hSNF5 regulates multiple pathways and genes including cyclinD1/cdk/p16 pathway, mitotic checkpoint, interferon signaling and hedgehog signaling in RTs cells (11,12,14,15,41). Here, we have shown, for the first time, that INI1/hSNF5 represses Aurora A selectively in RT cells.…”

The SWI/SNF complex and cancer

“…BAF155 has been shown to stabilize BAF47, BRG1 and BAF60A by attenuating their proteosomal degradation (Sohn et al, 2007). BAF155 may be phosphorylated by Akt, suggesting that PI3K/Akt signaling may modulate SWI/SNF function (Foster et al, 2006). Loss of BAF155 has been reported in a small number of cancer cell lines .…”

PKB/Akt-dependent regulation of inflammation in cancer

“…Colony stimulating factor (CSF-1) is another main driving cytokine for macrophage recruitment [102], which is transcriptional controlled by the SWI/SNF complex [108]. Although members of the SWI/SNF chromatin-remodeling complex have been shown to interact with and be phosphorylated by PKB [109], a direct contribution of PKB in the context of SWI/SNF mediated CSF-1 expression is still missing. Nonetheless, PKB has been shown to be required for macrophage chemotaxis in response to both CSF-1 and CCL2 [110].…”