Poriferan survivin exhibits a conserved regulatory role in the interconnected pathways of cell cycle and apoptosis
Poriferan survivin exhibits a conserved regulatory role in the interconnected pathways of cell cycle and apoptosis
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DOI：
10.1038/cdd.2010.87
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发表时间：
2011-02-01
影响因子：
12.4
通讯作者：
Wiens, M.
中科院分区：
文献类型：
--
作者：
Luthringer, B.;Isbert, S.;Wiens, M.
Survivin在细胞分裂和凋亡过程中协调细胞内通路。它作为有丝分裂调节剂和细胞死亡抑制剂的中心功能对肿瘤细胞增殖具有重要意义。到目前为止，对早期分支后生动物的分析表明，存活素作为染色体客运蛋白的排他作用，而只有在后来的进化过程中，随着生物体复杂性的增加，一种互补的抗凋亡功能才可能出现。为了揭开这个关键调节因子的祖先功能的面纱，我们鉴定了一个最早分支的后生动物分类群的存活蛋白样蛋白（SURVL）并对其进行了功能表征。海绵海绵海绵的SURVL与其后生同源物具有相当大的相似性，从保守的外显子/内含子结构到存在蛋白质相互作用域。而海绵组织显示出低稳态水平，SURVL表达在快速增殖的原始细胞中显著上调。此外，用重金属或脂肽刺激组织和原形刺激SURVL表达，同时也刺激新发现的caspase的表达。在转染的HEK-293细胞中进行的互补功能分析显示，SURVL-EFGP融合的异源表达不仅促进了细胞增殖，而且增强了对镉诱导的细胞死亡的抵抗力。综上所述，这些结果表明，survivin在进化中具有深层保守的双重作用，在细胞周期和细胞凋亡的相互联系途径中也具有同样保守的中心地位。细胞死亡与分化（2011）18,201-213；doi: 10.1038 / cdd.2010.87;2010年7月23日在线发布
Survivin orchestrates intracellular pathways during cell division and apoptosis. Its central function as mitotic regulator and inhibitor of cell death has major implications for tumor cell proliferation. Analyses in early-branching Metazoa so far propose an exclusive role of survivin as a chromosomal passenger protein, whereas only later during evolution a complementary antiapoptotic function might have arisen, concurrent with increased organismal complexity. To lift the veil on the ancestral function(s) of this key regulator, a survivin-like protein (SURVL) of one of the earliest-branching metazoan taxa was identified and functionally characterized. SURVL of the sponge Suberites domuncula shares considerable similarities with its metazoan homologs, ranging from conserved exon/intron structure to presence of protein-interaction domains. Whereas sponge tissue shows a low steady-state level, SURVL expression was significantly upregulated in rapidly proliferating primmorph cells. In addition, challenge of tissue and primmorphs with heavy metal or lipopeptide stimulated SURVL expression, concurrent with the expression of a newly discovered caspase. Complementary functional analyses in transfected HEK-293 cells revealed that heterologous expression of a SURVL-EFGP fusion not only promotes proliferation but also enhances resistance to cadmium-induced cell death. Taken together, these results suggest both a deep evolutionary conserved dual role of survivin and an equally conserved central position in the interconnected pathways of cell cycle and apoptosis. Cell Death and Differentiation (2011) 18, 201-213; doi: 10.1038/cdd.2010.87; published online 23 July 2010