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Identification and Developmental Expression of Xenopus laevis SUMO Proteases
Wang, Yonggang Mukhopadhyay, Debaditya Mathew, Smita Hasebe, Takashi Heimeier, Rachel A. Azuma, Yoshiaki Kolli, Nagamalleswari Shi, Yun-bo Wilkinson, Keith D. Dasso, Mary
Wang, Yonggang
Mukhopadhyay, Debaditya
Mathew, Smita
Hasebe, Takashi
Heimeier, Rachel A.
Azuma, Yoshiaki
Kolli, Nagamalleswari
Shi, Yun-bo
Wilkinson, Keith D.
Dasso, Mary
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Abstract
SUMO proteins are small ubiquitin-related modifiers. All SUMOs are synthesized as propeptides that are post-translationally cleaved prior to conjugation. After processing, SUMOs become covalently conjugated to cellular targets through a pathway that is similar to ubiquitination. Ubiquitin like protein proteases/Sentrin specific proteases (Ulp/SENPs) mediate both processing and deconjugation of SUMOs. The action of Ulp/SENPs makes SUMOylation a highly dynamic post-translational modification. To investigate how Ulp/SENPs are regulated in a developmental context, we isolated and characterized all Ulp/SENPs in Xenopus laevis. Xenopus possess homologues of mammalian SENP3, 5, 6 and 7. All of these enzymes reacted with HA-tagged vinyl sulfone derivatives of SUMO-2 (HA-SU2-VS) but not SUMO-1 (HA-SU1-VS), suggesting that they act primarily on SUMO-2 and -3. In contrast, Xenopus possess a single member of the SENP1/SENP2 subfamily of Ulp/SENPs, most closely related to mammalian SENP1. Xenopus SENP1 reacted with HA-SU1-VS and HA-SU2-VS, suggesting that it acts on all SUMO paralogues. We analyzed the mRNA and protein levels for each of the Ulp/SENPs through development; we found that they show distinct patterns of expression that may involve both transcriptional and post-transcriptional regulation. Finally, we have characterized the developmental function of the most abundant Ulp/SENP found within Xenopus eggs, SENP3. Depletion of SENP3 using morpholino antisense oligonucleotides (morpholinos) caused accumulation of high molecular weight SUMO-2/3 conjugated species, defects in developing embryos and changes in the expression of some genes regulated by the transforming growth factor beta (TGF-β) pathway. These findings collectively indicate that SUMO proteases are both highly regulated and essential for normal development.
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Date
2009-12-24
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Public Library of Science
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Keywords
Complementary DNA, Embryos, Messenger RNA, Morpholino, Proteases, Sequence databases, Sulfones, Xenopus
Citation
Wang Y, Mukhopadhyay D, Mathew S, Hasebe T, Heimeier RA, et al. (2009) Identification and Developmental Expression of Xenopus laevis SUMO Proteases. PLoS ONE 4(12): e8462. https://dx.doi.org/10.1371/journal.pone.0008462