Multi-tasking Sulf1/Sulf2 enzymes do not only facilitate extracellular cell Signalling but also participate in cell cycle related nuclear events

Multi-tasking Sulf1/Sulf2 enzymes do not only facilitate extracellular cell Signalling but also participate in cell cycle related nuclear events
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DOI:
10.1016/j.yexcr.2018.01.022
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发表时间:
2018-03-01
影响因子:
3.7
通讯作者:
Dhoot, Gurtej K.
Dhoot, Gurtej K.
中科院分区:
医学3区
文献类型:
--
作者:
Krishnakumar, Kavithanjali;Chakravorty, Ishani;Dhoot, Gurtej K.

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这项研究表明,SULF 1/SULF 2表达的高度动态的空间和时间模式,在正常培养基中生长的神经元细胞类型,包括他们的短暂的核动员。它们的核转位在细胞增殖期间变得特别明显,因为SULF 1/SULF 2不仅表现出细胞膜相关表达,它们的已知功能位点,而且还表现出核细胞分裂期间的瞬时核动员。核定位是明显的,不仅通过免疫细胞化学染色,但也证实了C6,U87和N2 A细胞的分离的核组分的免疫印迹染色。免疫细胞化学分析表明,细胞分裂后,SULF 1/SULF 2的快速核出口略有延迟,但在C6细胞中观察到的多倍体细胞的一部分中没有被阻断。C6和U87细胞中Sulf 1和Sulf 2基因的过表达显著促进这些细胞的体外生长,伴随着核动员,而抑制这两个基因抑制细胞增殖,很少或没有核SULF 1/SULF 2动员。因此,这些细胞中的SULF 1/SULF 2活性证明了细胞外细胞信号传导与细胞增殖相关的核事件的明确协调。
This study demonstrates highly dynamic spatial and temporal pattern of SULF1/SULF2 expression in a number of neuronal cell types growing in normal culture medium that included their transient nuclear mobilisation. Their nuclear translocation became particularly apparent during cell proliferation as both SULF1/SULF2 demonstrated not only cell membrane associated expression, their known site of function but also transient nuclear mobilisation during nuclear cell division. Nuclear localisation was apparent not only by immunocytochemical staining but also confirmed by immunoblotting staining of isolated nuclear fractions of C6, U87 and N2A cells. Immunocytochemical analysis demonstrated rapid nuclear exit of both SULF1/SULF2 following cell division that was slightly delayed but not blocked in a fraction of the polyploid cells observed in C6 cells. The overexpression of both Sulf1 and Sulf2 genes in C6 and U87 cells markedly promoted in vitro growth of these cells accompanied by nuclear mobilisation while inhibition of both these genes inhibited cell proliferation with little or no nuclear SULF1/SULF2 mobilisation. SULF1/SULF2 activity in these cells thus demonstrated a clear co-ordination of extracellular cell signalling with nuclear events related to cell proliferation.