SUMO-1 modification regulates the DNA binding activity of heat shock transcription factor 2, a promyelocytic leukemia nuclear body associated transcription factor

Heat shock transcription factor 2 (HSF2) is a transcription factor that reg ulates heat shock protein gene expression, but the mechanisms regulating th e function of this factor are unclear, Here we report that HSF2 is a substr ate for modification by the ubiquitin-related protein SUMO-1 and that HSF2 colocalizes in cells with SUMO-1 in nuclear granules. Staining with anti-pr omyelocytic leukemia antibodies indicates that these HSF2-containing nuclea r granules are PML bodies. Our results identify lysine 82 as the major site of SUMO-1 modification in HSF2, which is located in a "wing" within the DN A-binding domain of this protein. Interestingly, SUMO-1 modification of HSF 2 results in conversion of this factor to the active DNA binding form. This is the first demonstration that SUMO-1 modification can directly alter the DNA binding ability of a transcription factor and reveals a new mechanism by which SUMO-1 modification can regulate protein function.