Partial inactivation of the chromatin remodelers SMARCA2 and SMARCA4 in virus-infected cells by caspase-mediated cleavage

Dudek, Alexandra H.; Pfaff, Florian GND; Bolte, Hardin; Waguia Kontchou, Collins; Schwemmle, Martin

The BAF-chromatin remodeling complex with its mutually exclusive ATPases SMARCA2 and SMARCA4 is essential for the transcriptional activation of numerous genes, including a subset of interferon stimulated genes (ISGs). Here we show that C-terminally truncated forms of both SMARCA2 and SMARCA4 accumulate in cells infected with different RNA or DNA viruses. The levels of truncated SMARCA2 or SMARCA4 strongly correlate with the degree of cell damage and death observed after virus infection. The use of a pan-caspase inhibitor and genetically modified cell lines unable to undergo apoptosis revealed that the truncated forms result from the activity of caspases downstream of the activated intrinsic apoptotic pathway. C-terminally cleaved SMARCA2 and SMARCA4 lack potential nuclear localization signals as well as the bromo- and SnAC domain, the latter two domains believed to be essential for chromatin association and remodeling. Consistently, C-terminally truncated SMARCA2 was partially relocated to the cytoplasm. However, the remaining nuclear protein was sufficient to induce ISG expression and inhibit the replication of vesicular stomatitis virus and influenza A virus. This suggests that virus-induced apoptosis does not occur at the expense of an intact interferon-mediated antiviral response pathway.

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Dudek, Alexandra / Pfaff, Florian / Bolte, Hardin / et al: Partial inactivation of the chromatin remodelers SMARCA2 and SMARCA4 in virus-infected cells by caspase-mediated cleavage. 2018.

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