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Review
. 2009 Sep;66(18):3029-41.
doi: 10.1007/s00018-009-0061-z. Epub 2009 Jun 13.

PIAS proteins: pleiotropic interactors associated with SUMO

Miia M Rytinki  1 , Sanna Kaikkonen, Petri Pehkonen, Tiina Jääskeläinen, Jorma J Palvimo
Affiliations
Review

PIAS proteins: pleiotropic interactors associated with SUMO

Miia M Rytinki et al. Cell Mol Life Sci. 2009 Sep.

Abstract

The interactions and functions of protein inhibitors of activated STAT (PIAS) proteins are not restricted to the signal transducers and activators of transcription (STATs), but PIAS1, -2, -3 and -4 interact with and regulate a variety of distinct proteins, especially transcription factors. Although the majority of PIAS-interacting proteins are prone to modification by small ubiquitin-related modifier (SUMO) proteins and the PIAS proteins have the capacity to promote the modification as RING-type SUMO ligases, they do not function solely as SUMO E3 ligases. Instead, their effects are often independent of their Siz/PIAS (SP)-RING finger, but dependent on their capability to noncovalently interact with SUMOs or DNA through their SUMO-interacting motif and scaffold attachment factor-A/B, acinus and PIAS domain, respectively. Here, we present an overview of the cellular regulation by PIAS proteins and propose that many of their functions are due to their capability to mediate and facilitate SUMO-linked protein assemblies.

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Figures

Fig. 1
Fig. 1
SUMO modification pathway. SUMO proteins are C-terminally processed by a SUMO-specific protease (SENP) prior to attachment to the activating enzyme (SAE1/SAE2) and transfer to the conjugating E2 (Ubc9) enzyme. Ligation to target proteins is assisted by E3 ligases, such as PIAS proteins. Depending whether the target is modified by mono- or polySUMOylation, two alternative fates of the substrates are illustrated: MonoSUMOylation regulates the function, interaction or cellular localization of the substrate, whereas polySUMOylated protein is recognized by a SUMO-targeted ubiquitin ligase, such as RNF4, subsequently ubiquitylated and directed to proteasomal degradation
Fig. 2
Fig. 2
Schematic structures of PIAS proteins. The domain structures and post-translational modifications of the different human PIAS proteins are illustrated. Orthologous PIAS proteins from S. cerevisiae, C. elegans and D. melanogaster are also shown. Numbers on the right depict the amino acids in each PIAS protein
Fig. 3
Fig. 3
Network of experimentally observed protein–protein interactions between the four human PIAS proteins and their first interacting partners. Yellow and red nodes represent the PIAS proteins and the three SUMO proteins, respectively. Proteins that participate in the biological processes related to post-translational modifications and transcription have been marked with pink and green sectors, respectively. The graph was created using the APID2NET plugin [132] included in the Cytoscape software [133], which integrates BIND [134], BioGrid [135], DIP [136], HPRD [137], IncAct [138] and MINT [139] interaction databases. The graph is based on 120 proteins and 596 protein–protein interactions. The interacting proteins are listed in Supplementary Table 1
Fig. 4
Fig. 4
Functional modes of PIAS proteins in transcriptional regulation. Schematic models for different SP-RING-dependent mechanisms (a–d) and SIM- or SAP-dependent mechanisms (e and f, respectively) utilized by PIAS proteins. See text for examples of PIAS-interacting partners and details
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