SUSP1 antagonizes formation of highly SUMO2/3-conjugated species

Debaditya Mukhopadhyay, Ferhan Ayaydin, Nagamalleswari Kolli, Shyh Han Tan, Tadashi Anan, Ai Kametaka, Yoshiaki Azuma, Keith D. Wilkinson, Mary Dasso*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

129 Scopus citations


Small ubiquitin-related modifier (SUMO) processing and deconjugation are mediated by sentrin-specific proteases/ubiquitin-like proteases (SENP/Ulps). We show that SUMO-specific protease 1 (SUSP1), a mammalian SENP/Ulp, localizes within the nucleoplasm. SUSP1 depletion within cell lines expressing enhanced green fluorescent protein (EGFP) fusions to individual SUMO paralogues caused redistribution of EGFP-SUMO2 and -SUMO3, particularly into promyelocytic leukemia (PML) bodies. Further analysis suggested that this change resulted primarily from a deficit of SUMO2/3-deconjugation activity. Under these circumstances, PML bodies became enlarged and increased in number. We did not observe a comparable redistribution of EGFP-SUMO1. We have investigated the specificity of SUSP1 using vinyl sulfone inhibitors and model substrates. We found that SUSP1 has a strong paralogue bias toward SUMO2/3 and that it acts preferentially on substrates containing three or more SUMO2/3 moieties. Together, our findings argue that SUSP1 may play a specialized role in dismantling highly conjugated SUMO2 and -3 species that is critical for PML body maintenance.

Original languageEnglish
Pages (from-to)939-949
Number of pages11
JournalJournal of Cell Biology
Issue number7
StatePublished - 25 Sep 2006
Externally publishedYes


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