A new RING for SUMO: wrestling transcriptional responses into nuclear bodies with PIAS family E3 SUMO ligases (original) (raw)

  1. Peter K. Jackson1
  2. Department of Pathology and Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California 94305-5324, USA

Ubiquitin is known for its catabolic role in directing protein degradation when added to proteins in polyubiquitin chains, causing the targeted proteins to bind to and be degraded by the 26S proteasome. But when added as a monomer, ubiquitin can play an important role in noncatabolic processes ranging from histone regulation and endocytosis to virus budding (for review, seeHicke 2001). Recently a number of ubiquitin-like molecules (Ubls), including the protein SUMO (smallubiquitin-related modifier; also called sentrin), Nedd8/Rub1, and several even more exotic Ubls (Muller et al. 2001; Ohsumi 2001), have been found added to target proteins through isopeptide bonds to lysine side chains. Here, monoubiquitin and its Ubl cousins appear to function as posttranslational modifiers of protein function and likely reflect a more ancestral role for the ubiquitin structural fold in regulating protein activity. The biological roles of Ubl modification range even more broadly. Notably, modification by SUMO can play critical roles in both nuclear and cytoplasmic processes, including nuclear transport, the regulation of transcriptional processes, the targeting of transcriptional regulators to subnuclear domains, and the regulation of mitosis (Melchior and Hengst 2000;Hochstrasser 2001; Muller et al. 2001). Recently, an exciting new class of enzymes regulating the addition of SUMO to target proteins, called SUMO E3 ligases, has been described in yeast and mammals (Johnson and Gupta 2001; Kahyo et al. 2001; Takahashi et al. 2001). In this issue of Genes & Development, Sachdev and colleagues from the Grosschedl laboratory report that a member of this family of proteins, called PIASy, regulates the activity and subnuclear localization of the Wnt-responsive transcription factor LEF1 by directing SUMO addition to LEF1 (Sachdev et al. 2001). The implication is that this family of SUMO modifying enzymes may regulate a variety of …