HuR translocation to the cytoplasm of cancer cells in actin-independent manner
| Autor: | Masanobu Shindoh, Elora Hossain, Takeshi Kuroshima, Fumihiro Higashino, Yoshimasa Kitagawa, Jumond P. Jehung, Hidehiko Sano, Aya Yanagawa-Matsuda, Umma Habiba, Tetsuya Kitamura, Abu Faem Mohammad Almas Chowdhury |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Cytoplasm 3 '-untranslated region (3 '-UTR) RNA Stability Latrunculin A (LatA) Biology Myosins Microfilament Heterocyclic Compounds 4 or More Rings ELAV-Like Protein 1 03 medical and health sciences 0302 clinical medicine Cell Line Tumor Neoplasms Myosin Humans RNA Messenger Cytoskeleton ARE AU-rich element 3' Untranslated Regions Actin Blebbistatin (blebbistat) HuR human antigen R Cell Biology Hep G2 Cells Bridged Bicyclo Compounds Heterocyclic Angiotensin II Actins Cell biology Protein Transport 030104 developmental biology 030220 oncology & carcinogenesis COX-2 cyclooxygenase-2 Cancer cell Thiazolidines Human Angiotensin II (Ang.II) Intracellular HeLa Cells Protein Binding |
| Zdroj: | Experimental cell research. 369(2) |
| ISSN: | 1090-2422 |
| Popis: | Human antigen R (HuR) is a RNA-binding protein, which binds to the AU-rich element (ARE) in the 3'-untranslated region (3'-UTR) of certain mRNA and is involved in the export and stabilization of ARE-mRNA. HuR constitutively relocates to the cytoplasm in many cancer cells, however the mechanism of intracellular HuR trafficking is poorly understood. To address this question, we examined the functional role of the cytoskeleton in HuR relocalization. We tested the effect of actin depolymerizing macrolide latrunculin A or myosin II ATPase activity inhibitor blebbistatin for HuR relocalization induced by the vasoactive hormone Angiotensin II in cancer and control normal cells. Western blot and confocal imaging data revealed that both inhibitors attenuated the cytoplasmic HuR in normal cells but no such alteration was observed in cancer cells. Concomitant with changes in intracellular HuR localization, both inhibitors markedly decreased the accumulation and half-lives of HuR target ARE-mRNAs in normal cells, whereas no change was observed in cancer cells. Furthermore, co-immunoprecipitation experiments with HuR proteins revealed clear physical interaction with beta-actin only in normal cells. The current study is the first to verify that cancer cells can implicate a microfilament independent HuR transport. We hypothesized that when cytoskeleton structure is impaired, cancer cells can acquire an alternative HuR trafficking strategy. |
| Databáze: | OpenAIRE |
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