SUMOylation controls stem cell proliferation and regional cell death through Hedgehog signaling in planarians.

SUMOylation controls stem cell proliferation and regional cell death through Hedgehog signaling in planarians.
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DOI:
10.1007/s00018-017-2697-4
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发表时间:
2018-04
期刊:
Cellular and molecular life sciences : CMLS
影响因子:
--
通讯作者:
Oviedo NJ
Oviedo NJ
中科院分区:
其他
文献类型:
--
作者:
Thiruvalluvan M;Barghouth PG;Tsur A;Broday L;Oviedo NJ

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成人组织维持和再生过程中前后体轴差异的机制尚不清楚。在这里,我们发现通过SUMO(小泛素样修饰物)机制进行的翻译后修饰在地中海施米德虫中是进化保守的。通过唯一的SUMO E2偶联酶Ubc9的rna干扰破坏成年动物的SUMO酰化,导致DNA损伤的全身性增加和显著的区域缺陷,其特征是细胞死亡增加和身体后半部的丧失。我们发现Ubc9主要表达于虫干细胞(新生细胞),但也在分化细胞(包括神经元)中转录。Ubc9(RNAi)动物的再生受损并与低新细胞增殖相关。我们提供的证据表明,在ubc9诱导的区域细胞死亡之前,Hedgehog信号通路的抑制因子和激活因子的转录和空间表达发生了变化。我们的研究结果表明,在组织更新和再生过程中,SUMOylation作为一个区域特异性线索来调节细胞命运。summoylation控制区域细胞的命运
Mechanisms underlying anteroposterior body axis differences during adult tissue maintenance and regeneration are poorly understood. Here, we identify that post-translational modifications through the SUMO (Small Ubiquitin-like Modifier) machinery are evolutionarily conserved in the Lophotrocozoan Schmidtea mediterranea. Disruption of SUMOylation in adult animals by RNA-interference of the only SUMO E2 conjugating enzyme Ubc9 leads to systemic increase in DNA damage and a remarkable regional defect characterized by increased cell death and loss of the posterior half of the body. We identified that Ubc9 is mainly expressed in planarian stem cells (neoblasts) but it is also transcribed in differentiated cells including neurons. Regeneration in Ubc9(RNAi) animals is impaired and associated with low neoblast proliferation. We present evidence indicating that Ubc9-induced regional cell death is preceded by alterations in transcription and spatial expression of repressors and activators of the Hedgehog signaling pathway. Our results demonstrate that SUMOylation acts as a regional-specific cue to regulate cell fate during tissue renewal and regeneration. SUMOylation controls regional cell fate
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Ubc9 与核定位信号相互作用并介导成对同源染色体蛋白 Vsx-1 的核定位,与 SUMO-1 修饰无关
DOI: 10.1073/pnas.101129698
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影响因子: 11.1
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通讯作者: Schechter, N