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野生型、dEX3和2B存活素亚型定位于肿瘤细胞质膜,分泌于外泌体中,并与细胞外微管蛋白相互作用。

Wild type, dEX3 and 2B survivin isoforms localize to the tumor cell plasma membrane, are secreted in exosomes, and interact with extracellular tubulin.

作者信息

Figel Sheila, Birkemeier Meaghan, Dharma Sanam Sahjram, Barone Tara, Steinmetz Emma, Ciesielski Michael, Fenstermaker Robert

机构信息

Department of Neuro Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA.

Department of Pharmacology and Therapeutics, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA.

出版信息

Biochem Biophys Rep. 2021 Nov 20;28:101174. doi: 10.1016/j.bbrep.2021.101174. eCollection 2021 Dec.

Abstract

The Inhibitor of Apoptosis Protein survivin (svn) is upregulated in nearly all types of cancer and represents a promising therapeutic target. Localization to specific subcellular compartments and interactions with various binding partners allow survivin to play diverse roles in apoptosis resistance and mitosis. Survivin has recently been found in two extracellular compartments: the outer plasma membrane and secreted exosomes. In addition to svn-wt, splice variants svn-dEX3 and svn-2B are also overexpressed in human tumors. Here we show that, similarly to svn-wt, svn-dEX3 and svn-2B can be displayed on the outer plasma membrane, and secreted in exosomes. Additionally, we have identified a novel interaction of all three forms of survivin with secreted tubulin.

摘要

凋亡抑制蛋白survivin(svn)在几乎所有类型的癌症中均上调,是一个很有前景的治疗靶点。定位于特定的亚细胞区室并与各种结合伴侣相互作用,使survivin在抗凋亡和有丝分裂中发挥多种作用。最近在两个细胞外区室中发现了survivin:外质膜和分泌的外泌体。除了svn-wt,剪接变体svn-dEX3和svn-2B在人类肿瘤中也过表达。在此我们表明,与svn-wt类似,svn-dEX3和svn-2B可以展示在外质膜上,并分泌到外泌体中。此外,我们还发现了三种形式的survivin与分泌型微管蛋白之间的新型相互作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6748/8608592/8c05ba9a1f7c/gr1.jpg

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