Screen for multi-SUMO–binding proteins reveals a multi-SIM–binding mechanism for recruitment of the transcriptional regulator ZMYM2 to chromatin

Aguilar‐Martínez, Elisa; Chen, Xi; Webber, Aaron; Mould, A. Paul; Seifert, Adrian M.; Hay, Ronald T.; Sharrocks, Andrew D.

doi:10.1073/pnas.1509716112

Cited by 48 publications

(87 citation statements)

References 56 publications

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“…S1). Eleven of these 13 previously identified SUMO-binding proteins were found by two SUMO2-focused affinity purification and mass spectrometry based screens (29,35). The four SUMO protein probes that we tested showed wide variation in their binding specificity ( Fig.…”

Section: Identification Of Sumo-binding Partners Using Huprotmentioning

confidence: 98%

Global Analysis of SUMO-Binding Proteins Identifies SUMOylation as a Key Regulator of the INO80 Chromatin Remodeling Complex

Cox

Hwang

Uzoma

et al. 2017

Molecular & Cellular Proteomics

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SUMOylation is a critical regulator of a broad range of cellular processes, and is thought to do so in part by modulation of protein interaction. To comprehensively identify human proteins whose interaction is modulated by SUMOylation, we developed an binding assay using human proteome microarrays to identify targets of SUMO1 and SUMO2. We then integrated these results with protein SUMOylation and protein-protein interaction data to perform network motif analysis. We focused on a single network motif we termed a SUMOmodPPI (SUMO-modulated Protein-Protein Interaction) that included the INO80 chromatin remodeling complex subunits TFPT and INO80E. We validated the SUMO-binding activity of INO80E, and showed that TFPT is a SUMO substrate both and We then demonstrated a key role for SUMOylation in mediating the interaction between these two proteins, both and By demonstrating a key role for SUMOylation in regulating the INO80 chromatin remodeling complex, this work illustrates the power of bioinformatics analysis of large data sets in predicting novel biological phenomena.

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Section: Identification Of Sumo-binding Partners Using Huprotmentioning

confidence: 98%

Global Analysis of SUMO-Binding Proteins Identifies SUMOylation as a Key Regulator of the INO80 Chromatin Remodeling Complex

Cox

Hwang

Uzoma

et al. 2017

Molecular & Cellular Proteomics

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“…Likewise, Arkadia/RNF111 can independently ubiquitylate PML in response to its poly‐SUMOylation . However, multi‐SIM‐containing proteins may also serve to bind a protein with multiple mono‐SUMOylations or a protein complex with a multiSUMOylation pattern spread across the subunits . It remains poorly understood how multi‐SIM proteins achieve a preference for binding either a SUMO chain or multiple single SUMOs.…”

Section: Introductionmentioning

confidence: 99%

A FRET Sensor to Monitor Bivalent SUMO–SIM Interactions in SUMO Chain Binding

Kost

Mootz

2017

ChemBioChem

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The small ubiquitin-like modifier (SUMO) can be assembled into polymeric chains as part of its diverse biochemical signal pattern upon conjugation to substrate proteins. SUMO chain recognition is facilitated by receptor proteins that contain at least two SUMO-interacting motifs (SIMs). Little is known about the structure of SUMO chains, both in an unliganded form and upon complexation with multi-SIM protein partners. A FRET sensor has been developed based on a linear dimer of human SUMO-2 as a minimal SUMO chain analogue. The synthetic acceptor and donor dyes were conjugated by maleimide and copper-catalyzed click chemistry to each of the two SUMO subunits. FRET changes were only observed in the presence of di- or multi-SIM ligands. Alteration of the short linker sequence between SIMs 2 and 3 of RNF4 showed a great tolerance, and hence, structural flexibility, of the SUMO dimer for bivalent binding of adjacent SIMs. The di-SUMO FRET sensor reports on the binding of SIM clusters of the proteins C5orf25 and SOBP; this suggest that these can bind to adjacent subunits of a SUMO chain. The developed FRET sensor will be a useful tool to study the importance of SIM and linker sequences, as well as biochemical and structural properties of SUMO chains and multi-SIM proteins.

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“…Whereas most targets bear a single SUMO moiety, some are modified with multiple SUMOs via iterative conjugation cycles. The additional SUMOs can be linked to other Lys residues in the target or built as a poly-SUMO chain onto a single target Lys (Tatham et al, 2001;Aguilar-Martinez et al, 2015). Although the sites of SUMO attachment are typically substrate specific, several consensus motifs have been detected, including CKXE (where C is a large hydrophobic residue and K is the Lys where SUMO is bound) and extended motifs containing phosphorylated or negatively charged residues (Hietakangas et al, 2006;Matic et al, 2010).…”

mentioning

confidence: 99%

Defining the SUMO System in Maize: SUMOylation Is Up-Regulated during Endosperm Development and Rapidly Induced by Stress

et al. 2016

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In response to abiotic and biotic challenges, plants rapidly attach small ubiquitin-related modifier (SUMO) to a large collection of nuclear proteins, with studies in Arabidopsis (Arabidopsis thaliana) linking SUMOylation to stress tolerance via its modification of factors involved in chromatin and RNA dynamics. Despite this importance, little is known about SUMOylation in crop species. Here, we describe the plant SUMO system at the phylogenetic, biochemical, and transcriptional levels with a focus on maize (Zea mays). In addition to canonical SUMOs, land plants encode a loosely constrained noncanonical isoform and a variant containing a long extension upstream of the signature b-grasp fold, with cereals also expressing a novel diSUMO polypeptide bearing two SUMO b-grasp domains in tandem. Maize and other cereals also synthesize a unique SUMO-conjugating enzyme variant with more restricted expression patterns that is enzymatically active despite a distinct electrostatic surface. Maize SUMOylation primarily impacts nuclear substrates, is strongly induced by high temperatures, and displays a memory that suppresses subsequent conjugation. Both in-depth transcript and conjugate profiles in various maize organs point to tissue/cell-specific functions for SUMOylation, with potentially significant roles during embryo and endosperm maturation. Collectively, these studies define the organization of the maize SUMO system and imply important functions during seed development and stress defense.

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Screen for multi-SUMO–binding proteins reveals a multi-SIM–binding mechanism for recruitment of the transcriptional regulator ZMYM2 to chromatin

Cited by 48 publications

References 56 publications

Global Analysis of SUMO-Binding Proteins Identifies SUMOylation as a Key Regulator of the INO80 Chromatin Remodeling Complex

Global Analysis of SUMO-Binding Proteins Identifies SUMOylation as a Key Regulator of the INO80 Chromatin Remodeling Complex

A FRET Sensor to Monitor Bivalent SUMO–SIM Interactions in SUMO Chain Binding

Defining the SUMO System in Maize: SUMOylation Is Up-Regulated during Endosperm Development and Rapidly Induced by Stress

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