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The neural ELAVL protein HuB enhances endogenous proto-oncogene activation

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Title: The neural ELAVL protein HuB enhances endogenous proto-oncogene activation
Authors: Hatanaka, Tomoyuki Browse this author
Higashino, Fumihiro Browse this author →KAKEN DB
Tei, Kanchu Browse this author →KAKEN DB
Yasuda, Motoaki Browse this author →KAKEN DB
Keywords: HuR
HuB
3 ' UTR
Proto-oncogene
Issue Date: 17-Sep-2019
Publisher: Elsevier
Journal Title: Biochemical and biophysical research communications
Volume: 517
Issue: 2
Start Page: 330
End Page: 337
Publisher DOI: 10.1016/j.bbrc.2019.07.089
Abstract: The cytoplasmic distribution of the HuR/ELAVL1 (embryonic lethal abnormal vision 1) protein is recognized as an important prognostic factor of malignant tumors. However, the previous study suggests that exogenous over-expression of HuR is not sufficient for nuclear export. Conversely, the predominantly cytosolic distribution of neuron-specific human ELAV members, including HuB/ELAVL2, HuC/ELAVL3, and HuD/ELAVL4, has been reported. In the present study, we demonstrated the expression of HuB in several types of cancer cells, but expression of HuC and HuD was not observed. In addition, our results indicated that HuR and HuB formed a complex in the cytosolic fraction of cancer cells via the RRM3 region. Ectopic expression of HuB was capable of initiating the cytosolic translocation of HuR from the nucleus to the cytosol. Furthermore, HuB-transduced cancer cells displayed significant nuclear export of HuR, with quantitative PCR experiments revealing the simultaneous upregulation of HIF-1 alpha, c-Fos, c-MYC, and Ets2 basal mRNA expression. Phorbol 12-myristate 13-acetate (PMA)-stimulated HuB-transduced cells demonstrated significantly enhanced activation of endogenous c-Fos and CREB dependent cascades. Finally, co-transfection of HuB with the El region of type 5 human adenovirus significantly enhanced El transformation activities but that of HuR with the El region did not. Collectively, our findings suggest that the neural Hu family protein HuB plays a major role in the activation of memory-related proto-oncogenes. (C) 2019 Elsevier Inc. All rights reserved.
Rights: © <2019>. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/
https://creativecommons.org/licenses/by-nc-nd/4.0/
Type: article (author version)
URI: http://hdl.handle.net/2115/79285
Appears in Collections:歯学院・歯学研究院 (Graduate School of Dental Medicine / Faculty of Dental Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 安田 元昭

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