摘要
到许多蛋白质的小 ubiquitin 相关的修饰词(相扑) 变化形式调整多样的细胞的过程,包括抄写,房间周期规定和染色体正直的维护。在 vivo 调查相扑 paralogs 的生物功能,我们在 zebrafish 的早开发使他们失去活性。当作为 Ubc9 缺乏的,为所有三相扑 paralogs 缺乏的 zebrafish 胚胎显示了严重缺点时,单个相扑 paralog 的损失与正常开发兼容。相扑缺乏的胚胎能被一个单个人或 zebrafish 相扑救。当关键时结构的基本离氨酸残余和 N 终端相扑的未组织的段是批评的为在 vivo 营救, SUMO2 的一致 K11 sumoylation 地点是非必需的,在这个潜在的地点上暗示那链形成为正常开发是非本质的。所有三相扑的 Inactivation 触发了 p53 依赖的 apoptosis, p53 的进一步的 inactivation 恢复了正常 zebrafish 开发。有趣地,我们也证明 p53 的主导的否定截断的形式,螖 1 13p53,显著地弄钝相扑在 vivo 的导致弄空的 p53 活动。一起拿,我们的结果建议相扑 paralogs 不可缺少,却冗余,在 zebrafish 的早发展。
The Small ubiquitin-related modifier (SUMO) conjugation to a variety of proteins regulates diverse cellular processes, including transcription, cell cycle regulation and maintenance of genome integrity. To investigate in vivo biological function of SUMO paralogs, we inactivated them in the early development of zebrafish. While zebrafish embryos deficient for all three SUMO paralogs, as Ubc9-deficient ones, displayed severe defects, loss of individual SUMO paralog was compatible with a normal development. SUMO-deficient embryos can be rescued by a single human or zebrafish SUMO. While key structural basic lysine residues and N-terminal unstructured stretch of SUMO are critical for in vivo rescue, the consensus Kll sumoylation site of SUMO2 is dispensable, implying that chain formation on this potential site is unessential for normal development. Inactivation of all three SUMOs triggered p53- dependent apoptosis and further inactivation of p53 restored normal zebrafish development. Interestingly, we also demonstrate that the dominant negative truncated form of p53, Δ113p53, significantly blunts SUMO depletion-induced p53 activity in vivo. Taken together, our results suggest that SUMO paralogs are indispensable, but redundant, in the early development of zebrafish.
基金
Supplementary information is linked to the online version of the paper on the Cell Research website.Acknowledgements We thank Dr Jiang Zhu (Shanghai institute of hematology, Rui Jin hospital) and Dr Nelly Kieffer (CNRS LIA, Rui Jin hospital) for their comments. This work was supported by grants from the National High Tech Program of China (863, 2006AA02Z150), the National Science Foundation of China (30525006), the Science and Technology Commission of Shanghai Municipality (07XD14022, 06PJ14068), ATIP program and BNP PARIBAS.