Identification and developmental expression of Xenopus laevis SUMO proteases.
Identification and developmental expression of Xenopus laevis SUMO proteases.
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DOI：
10.1371/journal.pone.0008462
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发表时间：
2009-12-24
期刊：
影响因子：
3.7
通讯作者：
Dasso M
中科院分区：
文献类型：
--
作者：
Wang Y;Mukhopadhyay D;Mathew S;Hasebe T;Heimeier RA;Azuma Y;Kolli N;Shi YB;Wilkinson KD;Dasso M
SUMO蛋白是小的泛素相关修饰物。所有的sumo都是作为前肽合成的，在缀合之前被翻译后切割。加工后，sumo通过类似泛素化的途径与细胞靶标共价结合。泛素样蛋白蛋白酶/Sentrin特异性蛋白酶（Ulp/SENPs）介导sumo的加工和解偶联。Ulp/SENPs的作用使SUMOylation成为一个高度动态的翻译后修饰。为了研究Ulp/SENPs在发育过程中是如何调控的，我们分离并表征了非洲爪蟾中所有的Ulp/SENPs。爪蟾具有哺乳动物SENP3、5、6和7的同源物。这些酶均能与ha标记的SUMO-2的乙烯砜衍生物（HA-SU2-VS）反应，但不能与SUMO-1 （HA-SU1-VS）反应，表明它们主要作用于SUMO-2和-3。相比之下，非洲爪蟾拥有Ulp/SENPs的SENP1/SENP2亚家族的一个成员，与哺乳动物SENP1最密切相关。Xenopus SENP1与HA-SU1-VS和HA-SU2-VS发生反应，表明它作用于所有的SUMO亲缘物。我们通过发育分析了每个Ulp/SENPs的mRNA和蛋白质水平；我们发现它们表现出不同的表达模式，可能涉及转录和转录后调控。最后，我们描述了在爪蟾卵中发现的最丰富的Ulp/SENP SENP3的发育功能。利用morpholinos反义寡核苷酸（morpholinos）去除SENP3可引起高分子量SUMO-2/3偶联种的积累，导致胚胎发育缺陷，并改变转化生长因子β (TGF-β)途径调控的部分基因的表达。这些发现共同表明，SUMO蛋白酶是高度调控的，对正常发育至关重要。
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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