GFZF, a glutathione S-transferase protein implicated in cell cycle regulation and hybrid inviability, is a transcriptional coactivator

The core promoters of protein-encoding genes play a central role in regulating transcription. M1BP is a transcriptional activator that associates with a core promoter element known as Motif 1 that resides at thousands of genes in Drosophila. To gain insight into how M1BP functions, we identified an interacting protein called GFZF. GFZF had been previously identified in genetic screens for factors involved in maintenance of hybrid inviability, the G ₂ -M DNA damage checkpoint, and RAS/mitogen-activated protein kinase (MAPK) signaling, but its contribution to these processes was unknown. Here, we show that GFZF resides in the nucleus and functions as a transcriptional coactivator. In addition, we show that GFZF is a glutathione S-transferase (GST). Thus, GFZF is the first transcriptional coactivator with intrinsic GST activity, and its identification as a transcriptional coactivator provides an explanation for its role in numerous biological processes.