SPOC1: a novel PHD-containing protein modulating chromatin structure and mitotic chromosome condensation
SPOC1: a novel PHD-containing protein modulating chromatin structure and mitotic chromosome condensation
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DOI：
10.1242/jcs.047365
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发表时间：
2009-08-15
影响因子：
4
通讯作者：
Will, Hans
中科院分区：
文献类型：
--
作者：
Kinkley, Sarah;Staege, Hannah;Will, Hans
在这项研究中，我们描述了一种新的蛋白质SPOC 1的分子和功能特征。SPOC 1 RNA表达在高度增殖组织中最高，在卵巢癌患者的一个亚组中增加，这与预后不良和残留疾病有统计学相关性。这些观察结果表明，SPOC1可能在细胞增殖和肿瘤发生中发挥作用。在这里，我们表明，内源性SPOC1蛋白是不稳定的，主要是染色质相关的，其表达以及本地化的整个细胞周期的调节。SPOC1在有丝分裂过程中受到动态调节，表达水平增加，并双相定位于有丝分裂染色体，表明SPOC1在有丝分裂过程中的功能作用。与这一假设相一致，SPOC1 siRNA敲除实验导致有丝分裂染色体凝聚，对齐和异常姐妹染色单体分离的缺陷。最后，我们已经能够表明，使用微球菌核酸酶（MNase）染色质消化试验，SPOC1的表达水平成比例地影响染色质压实的程度。总的来说，我们的研究结果表明，SPOC1调节染色质结构和有丝分裂过程中其表达水平和亚细胞定位的严格调控是正确的染色体凝聚和细胞分裂至关重要。
In this study, we characterize the molecular and functional features of a novel protein called SPOC1. SPOC1 RNA expression was previously reported to be highest in highly proliferating tissues and increased in a subset of ovarian carcinoma patients, which statistically correlated with poor prognosis and residual disease. These observations implied that SPOC1 might play a role in cellular proliferation and oncogenesis. Here we show that the endogenous SPOC1 protein is labile, primarily chromatin associated and its expression as well as localization are regulated throughout the cell cycle. SPOC1 is dynamically regulated during mitosis with increased expression levels and biphasic localization to mitotic chromosomes indicating a functional role of SPOC1 in mitotic processes. Consistent with this postulate, SPOC1 siRNA knockdown experiments resulted in defects in mitotic chromosome condensation, alignment and aberrant sister chromatid segregation. Finally, we have been able to show, using micrococcal nuclease (MNase) chromatin-digestion assays that SPOC1 expression levels proportionally influence the degree of chromatin compaction. Collectively, our findings show that SPOC1 modulates chromatin structure and that tight regulation of its expression levels and subcellular localization during mitosis are crucial for proper chromosome condensation and cell division.