PIAS proteins and transcriptional regulation--more than just SUMO E3 ligases?

The PIAS family of proteins was named based on the identification of the founding member, PIAS3, as a repressor of the activity of the STAT3 transcription factor (Protein Inhibitor of Activated STAT) (Chung et al. 1997). Since then, three additional family members— PIAS1, PIASy, and PIASx—have been identified and are characterized by a high degree of sequence conservation throughout the proteins (for review, see Schmidt and Muller 2003; Shuai and Liu 2005). Additional proteins exist with more limited similarity, including hZIMP7 and hZIMP10 (Sharma et al. 2003; Huang et al. 2005). PIAS proteins have been shown to impact on the function of many different proteins, but a major process on which all these proteins act is in controlling gene transcription. Thus, PIAS proteins can be thought of as transcriptional coregulators. PIAS protein action can either be activating or repressive, although their mechanism of action apparently differs depending on the target gene or interacting transcriptional regulator (for review, see Schmidt and Muller 2003; Shuai and Liu 2005). One major mechanism through which PIAS proteins operate appears to be through the relocalization of transcriptional regulators to different subnuclear compartments. In this issue of Genes & Development, further weight to this particular mechanism is provided, as PIAS1 is shown to localize the Msx1 homeodomain transcription factor to the nuclear periphery (Lee et al. 2006). This localization is thought to be instrumental in permitting Msx1 to engage with its target promoters and hence cause their repression. However, several other mechanisms of action have been shown for PIAS proteins, although these are not necessarily mutually exclusive with a role in controlling the subcellular localization of target proteins.