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UNC-45A 在上皮细胞中优先表达,并与有丝分裂期 MT 结合并共定位。

UNC-45A is preferentially expressed in epithelial cells and binds to and co-localizes with interphase MTs.

机构信息

Masonic Cancer Center and Department of Obstetrics, Gynecology and Women's Heath, University of Minnesota , Minneapolis , MN , USA.

Department of Medicine, Brandenburg Medical School Theodor Fontane , Neuruppin , Germany.

出版信息

Cancer Biol Ther. 2019;20(10):1304-1313. doi: 10.1080/15384047.2019.1632637. Epub 2019 Jul 22.

DOI:10.1080/15384047.2019.1632637
PMID:31328624
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6783119/
Abstract

UNC-45A is an ubiquitously expressed protein highly conserved throughout evolution. Most of what we currently know about UNC-45A pertains to its role as a regulator of the actomyosin system. However, emerging studies from both our and other laboratories support a role of UNC-45A outside of actomyosin regulation. This includes studies showing that UNC-45A: regulates gene transcription, co-localizes and biochemically co-fractionates with gamma tubulin and regulates centrosomal positioning, is found in the same subcellular fractions where MT-associated proteins are, and is a mitotic spindle-associated protein with MT-destabilizing activity in absence of the actomyosin system. Here, we extended our previous findings and show that UNC45A is variably expressed across a spectrum of cell lines with the highest level being found in HeLa cells and in ovarian cancer cells inherently paclitaxel-resistant. Furthermore, we show that UNC-45A is preferentially expressed in epithelial cells, localizes to mitotic spindles in clinical tumor specimens of cancer and co-localizes and co-fractionates with MTs in interphase cells independent of actin or myosin. In sum, we report alteration of UNC45A localization in the setting of chemotherapeutic treatment of cells with paclitaxel, and localization of UNC45A to MTs both and . These findings will be important to ongoing and future studies in the field that further identify the important role of UNC45A in cancer and other cellular processes.

摘要

UNC-45A 是一种普遍表达的蛋白质,在整个进化过程中高度保守。我们目前对 UNC-45A 的了解主要集中在它作为肌动球蛋白系统调节剂的作用上。然而,我们和其他实验室的新兴研究支持 UNC-45A 在肌动球蛋白调节之外的作用。这包括研究表明 UNC-45A:调节基因转录,与 γ 微管蛋白共定位和生化共分馏,并调节中心体定位,存在于与 MT 相关蛋白相同的亚细胞部分,并且是具有 MT 不稳定活性的有丝分裂纺锤体相关蛋白在没有肌动球蛋白系统的情况下。在这里,我们扩展了之前的发现,并表明 UNC45A 在一系列细胞系中表现出不同的表达谱,其中在 HeLa 细胞和卵巢癌细胞中表达水平最高,这些细胞对紫杉醇固有耐药。此外,我们表明 UNC-45A 优先在上皮细胞中表达,在癌症的临床肿瘤标本中的有丝分裂纺锤体中定位,并与 MT 在有丝分裂间期细胞中共定位和共分馏,而不依赖于肌动蛋白或肌球蛋白。总之,我们报告了在紫杉醇处理细胞的化疗治疗中 UNC45A 定位的改变,以及 UNC45A 向 MT 的定位。这些发现对于该领域正在进行和未来的研究将是重要的,这些研究将进一步确定 UNC45A 在癌症和其他细胞过程中的重要作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2a5/6783119/8040ed87d6d2/kcbt-20-10-1632637-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2a5/6783119/5ad05980f9c1/kcbt-20-10-1632637-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2a5/6783119/16a11c3b344d/kcbt-20-10-1632637-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2a5/6783119/d2a75d50d253/kcbt-20-10-1632637-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2a5/6783119/242d6558f774/kcbt-20-10-1632637-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2a5/6783119/8040ed87d6d2/kcbt-20-10-1632637-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2a5/6783119/5ad05980f9c1/kcbt-20-10-1632637-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2a5/6783119/16a11c3b344d/kcbt-20-10-1632637-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2a5/6783119/d2a75d50d253/kcbt-20-10-1632637-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2a5/6783119/242d6558f774/kcbt-20-10-1632637-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2a5/6783119/8040ed87d6d2/kcbt-20-10-1632637-g005.jpg

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本文引用的文献

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J Biol Chem. 2019 Apr 5;294(14):5246-5260. doi: 10.1074/jbc.RA118.006597. Epub 2019 Feb 8.
2
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Mol Cancer Res. 2019 Feb;17(2):370-383. doi: 10.1158/1541-7786.MCR-18-0670. Epub 2018 Oct 15.
3
Tipping microtubule dynamics, one protofilament at a time.
Cells. 2024 Jan 2;13(1):94. doi: 10.3390/cells13010094.
4
Expression of hub genes of endothelial cells in glioblastoma-A prognostic model for GBM patients integrating single-cell RNA sequencing and bulk RNA sequencing.内皮细胞枢纽基因在胶质母细胞瘤中的表达——整合单细胞 RNA 测序和批量 RNA 测序的 GBM 患者预后模型。
BMC Cancer. 2022 Dec 6;22(1):1274. doi: 10.1186/s12885-022-10305-z.
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6
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