CIZ1-F, an alternatively spliced variant of the DNA replication protein CIZ1 with distinct expression and localisation, is overrepresented in early stage common solid tumours.
CIZ1-F, an alternatively spliced variant of the DNA replication protein CIZ1 with distinct expression and localisation, is overrepresented in early stage common solid tumours.
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DOI：
10.1080/15384101.2018.1526600
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Coverley D
中科院分区：
文献类型：
--
作者：
Swarts DRA;Stewart ER;Higgins GS;Coverley D
CIZ1促进细胞周期蛋白依赖的DNA复制，存在于蛋白质核基质(NM)中的亚核中心，以及在女性细胞中不活跃的X染色体(XI)处富含的RNA组件中。它受到选择性剪接的影响，特定的变种与成人和儿童癌症有关。CIZ1-F的特征是剪接外显子8-12导致的帧移动，导致包含一个短的替代阅读框架(ARF)，不包括先前描述的C-末端NM锚定结构域。在这里，我们应用一套新的针对ARF的变体选择分子工具来分析CIZ1-F在转录和蛋白质水平上的表达，重点研究它与NM的RNA依赖和非依赖部分的关系。与全长CIZ1不同，CIZ1-F不会在XI积累，尽管像全长CIZ1一样，它确实抵抗DNase的提取。值得注意的是，CIZ1-F对RNase敏感，将其鉴定为NM的RNA组分的一部分。在静止细胞中，CIZ1-F转录本的表达被抑制，CIZ1-F蛋白被排除在细胞核之外，直到第二个细胞周期退出静止后才能观察到重新表达。重要的是，CIZ1-F在包括结肠癌和乳腺在内的常见实体肿瘤中过度表达，在早期明显，但在高增殖的晚期肿瘤中不明显。此外，激素受体阴性的乳腺肿瘤的表达显著高于受体阳性的肿瘤。综上所述，这些数据表明CIZ1-F以一种不寻常的细胞周期依赖的方式在增殖细胞中表达，并提示它可能作为一种潜在的肿瘤生物标记物。
CIZ1 promotes cyclin-dependent DNA replication and resides in sub-nuclear foci that are part of the protein nuclear matrix (NM), and in RNA assemblies that are enriched at the inactive X chromosome (Xi) in female cells. It is subjected to alternative splicing, with specific variants implicated in adult and pediatric cancers. CIZ1-F is characterized by a frame shift that results from splicing exons 8–12 leading to inclusion of a short alternative reading frame (ARF), excluding the previously characterized C-terminal NM anchor domain. Here, we apply a set of novel variant-selective molecular tools targeted to the ARF to profile the expression of CIZ1-F at both transcript and protein levels, with focus on its relationship with the RNA-dependent and -independent fractions of the NM. Unlike full-length CIZ1, CIZ1-F does not accumulate at Xi, though like full-length CIZ1 it does resist extraction with DNase. Notably, CIZ1-F is sensitive to RNase identifying it as part of the RNA-fraction of the NM. In quiescent cells CIZ1-F transcript expression is suppressed and CIZ1-F protein is excluded from the nucleus, with re-expression not observed until the second cell cycle after exit from quiescence. Importantly, CIZ1-F is over-expressed in common solid tumors including colon and breast, pronounced in early stage but not highly-proliferative late stage tumors. Moreover, expression was significantly higher in hormone receptor negative breast tumors than receptor positive tumors. Together these data show that CIZ1-F is expressed in proliferating cells in an unusual cell cycle-dependent manner, and suggest that it may have potential as a tumor biomarker.
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影响因子：
10.5
作者：
Ridings-Figueroa R;Stewart ER;Nesterova TB;Coker H;Pintacuda G;Godwin J;Wilson R;Haslam A;Lilley F;Ruigrok R;Bageghni SA;Albadrani G;Mansfield W;Roulson JA;Brockdorff N;Ainscough JFX;Coverley D
通讯作者：
Coverley D
影响因子：
64.8
作者：
Heery, DM;Kalkhoven, E;Parker, MG
通讯作者：
Parker, MG
Ciz1 促进前列腺癌细胞的致瘤性。
影响因子：
3.1
作者：
Liu, Tao;Ren, Xiaohui;Kong, Chuize
通讯作者：
Kong, Chuize
影响因子：
2.8
作者：
Coverley D;Higgins G;West D;Jackson OT;Dowle A;Haslam A;Ainscough E;Chalkley R;White J
通讯作者：
White J
影响因子：
11.2
作者：
den Hollander, Petra;Kumar, Rakesh
通讯作者：
Kumar, Rakesh