Novel proteomics strategy brings insight into the prevalence of SUMO-2 target sites

Henri A Blomster, Ville Hietakangas, Jianmin Wu, Petri Kouvonen, Sampsa Hautaniemi, Lea Sistonen

Tutkimustuotos: LehtiartikkeliArtikkeliTieteellinenvertaisarvioitu

77 Sitaatiot (Scopus)

Abstrakti

Small ubiquitin-like modifier (SUMO) is covalently conjugated to its target proteins thereby altering their activity. The mammalian SUMO protein family includes four members (SUMO-1-4) of which SUMO-2 and SUMO-3 are conjugated in a stress-inducible manner. The vast majority of known SUMO substrates are recognized by the single SUMO E2-conjugating enzyme Ubc9 binding to a consensus tetrapeptide (PsiKXE where Psi stands for a large hydrophobic amino acid) or extended motifs that contain phosphorylated or negatively charged amino acids called PDSM (phosphorylation-dependent sumoylation motif) and NDSM (negatively charged amino acid-dependent sumoylation motif), respectively. We identified 382 SUMO-2 targets using a novel method based on SUMO protease treatment that improves separation of SUMO substrates on SDS-PAGE before LC-ESI-MS/MS. We also implemented a software SUMOFI (SUMO motif finder) to facilitate identification of motifs for SUMO substrates from a user-provided set of proteins and to classify the substrates according to the type of SUMO-targeting consensus site. Surprisingly more than half of the substrates lacked any known consensus site, suggesting that numerous SUMO substrates are recognized by a yet unknown consensus site-independent mechanism. Gene ontology analysis revealed that substrates in distinct functional categories display strikingly different prevalences of NDSM sites. Given that different types of motifs are bound by Ubc9 using alternative mechanisms, our data suggest that the preference of SUMO-2 targeting mechanism depends on the biological function of the substrate.

AlkuperäiskieliEnglanti
Sivut1382–1390
Sivumäärä9
JulkaisuMolecular and Cellular Proteomics
Vuosikerta8
Numero6
DOI - pysyväislinkit
TilaJulkaistu - kesäk. 2009
OKM-julkaisutyyppiA1 Julkaistu artikkeli, soviteltu

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