The pericentromeric protein shugoshin 2 cooperates with HSF 1 in heat shock response and RNA Pol II recruitment

The recruitment of RNA polymerase II (Pol II ) to core promoters is highly regulated during rapid induction of genes. In response to heat shock, heat shock transcription factor 1 ( HSF 1) is activated and occupies heat shock gene promoters. Promoter‐bound HSF 1 recruits general transcription factors and Mediator, which interact with Pol II , but stress‐specific mechanisms of Pol II recruitment are unclear. Here, we show in comparative analyses of HSF 1 paralogs and their mutants that HSF 1 interacts with the pericentromeric adaptor protein shugoshin 2 ( SGO 2) during heat shock in mouse cells, in a manner dependent on inducible phosphorylation of HSF 1 at serine 326, and recruits SGO 2 to the HSP 70 promoter. SGO 2‐mediated binding and recruitment of Pol II with a hypophosphorylated C‐terminal domain promote expression of HSP 70 , implicating SGO 2 as one of the coactivators that facilitate Pol II recruitment by HSF 1. Furthermore, the HSF 1‐ SGO 2 complex supports cell survival and maintenance of proteostasis in heat shock conditions. These results exemplify a proteotoxic stress‐specific mechanism of Pol II recruitment, which is triggered by phosphorylation of HSF 1 during the heat shock response.