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Evaluating nuclear translocation of surface receptors: recommendations arising from analysis of CD44.
Histochemistry and Cell Biology ( IF 2.3 ) Pub Date : 2019-12-13 , DOI: 10.1007/s00418-019-01835-y
Rick F Thorne 1, 2 , Yan Wang 1 , Yan Zhang 1 , Xueli Jing 1 , Xu Dong Zhang 1, 3 , Charles E de Bock 4 , Camila S Oliveira 5
Affiliation  

CD44 is a transmembrane receptor that acts as adhesion protein, fundamentally recognizing hyaluronan, an essential component of the extracellular matrix. It has a well-established functional association with cancer metastasis, particularly the CD44 variant forms which are considered essential markers of cancer stem cells. CD44 itself lacks intrinsic kinase activity but rather engages in signalling through specific interactions with kinases and other signalling components. Proteolysis within its transmembrane region also leads to release of the CD44 cytoplasmic domain, which can translocate to the nucleus and regulate transcription. A third signalling modality has been reported where the intact CD44 receptor translocates to the nucleus. Here, we investigated the latter using imaging techniques together with biochemical analyses. Our findings support observations where CD44 is cleaved prior to nuclear translocation and challenges the evidence for the presence of intact CD44 receptors in the cell nucleus. Conclusions regarding the presence of intact CD44 in the cell nucleus as a signalling modality, therefore, require re-evaluation. We highlight artefacts and common technical issues associated with these experiments that can lead to misinterpretation.

中文翻译:

评估表面受体的核易位:从CD44分析中得出的建议。

CD44是一种跨膜受体,可作为粘附蛋白,从根本上识别透明质酸(透明质酸),它是细胞外基质的重要组成部分。它与癌症转移,特别是被认为是癌症干细胞的重要标志物的CD44变异形式,具有公认的功能关联。CD44本身缺乏内在的激酶活性,而是通过与激酶和其他信号传导成分的特异性相互作用参与信号传导。其跨膜区域内的蛋白水解还导致CD44胞质域的释放,该CD44可以转移到细胞核并调节转录。已经报道了第三种信号传导方式,其中完整的CD44受体易位至细胞核。在这里,我们使用成像技术与生化分析一起研究了后者。我们的发现支持观察到CD44在核易位之前先被切割的现象,并挑战了在细胞核中存在完整CD44受体的证据。因此,关于细胞核中完整CD44的存在作为信号传导方式的结论需要重新评估。我们重点介绍与这些实验相关的人工制品和常见技术问题,这些问题可能会导致误解。
更新日期:2019-12-13
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