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UBTOR/KIAA1024 regulates neurite outgrowth and neoplasia through mTOR signaling

The mTOR signaling pathways regulate cell growth and are involved in multiple human diseases. Here, we identify UBTOR, a previously unannotated gene as a functional player in regulating cell growth and mTOR signaling. Reduction of UBTOR function in cultured hippocampal neurons and PC12 cells promote...

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Detalles Bibliográficos
Autores principales: Zhang, Hefei, Zhang, Quan, Gao, Ge, Wang, Xinjian, Wang, Tiantian, Kong, Zhitao, Wang, Guoxiang, Zhang, Cuizhen, Wang, Yun, Peng, Gang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6095612/
https://www.ncbi.nlm.nih.gov/pubmed/30080879
http://dx.doi.org/10.1371/journal.pgen.1007583
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author Zhang, Hefei
Zhang, Quan
Gao, Ge
Wang, Xinjian
Wang, Tiantian
Kong, Zhitao
Wang, Guoxiang
Zhang, Cuizhen
Wang, Yun
Peng, Gang
author_facet Zhang, Hefei
Zhang, Quan
Gao, Ge
Wang, Xinjian
Wang, Tiantian
Kong, Zhitao
Wang, Guoxiang
Zhang, Cuizhen
Wang, Yun
Peng, Gang
author_sort Zhang, Hefei
collection PubMed
description The mTOR signaling pathways regulate cell growth and are involved in multiple human diseases. Here, we identify UBTOR, a previously unannotated gene as a functional player in regulating cell growth and mTOR signaling. Reduction of UBTOR function in cultured hippocampal neurons and PC12 cells promotes neurite outgrowth. UBTOR depletion activates mTOR signaling and promotes cell growth, whilst UBTOR overexpression suppresses colony formation in cancer cell lines. Studies in cultured cells and zebrafish model show that UBTOR inhibits mTOR signaling by stabilizing the mTOR complex component DEPTOR, and ubtor gene disruption result in higher mTOR activity and aggravate HRAS(G12V) induced neoplasia in the zebrafish. Lastly, UBTOR depletion promotes tumor growth and mTOR signaling in a xenograft mouse model. Together, our results demonstrate how UBTOR regulates cell growth and neoplasia via mTOR signaling.
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spelling pubmed-60956122018-08-30 UBTOR/KIAA1024 regulates neurite outgrowth and neoplasia through mTOR signaling Zhang, Hefei Zhang, Quan Gao, Ge Wang, Xinjian Wang, Tiantian Kong, Zhitao Wang, Guoxiang Zhang, Cuizhen Wang, Yun Peng, Gang PLoS Genet Research Article The mTOR signaling pathways regulate cell growth and are involved in multiple human diseases. Here, we identify UBTOR, a previously unannotated gene as a functional player in regulating cell growth and mTOR signaling. Reduction of UBTOR function in cultured hippocampal neurons and PC12 cells promotes neurite outgrowth. UBTOR depletion activates mTOR signaling and promotes cell growth, whilst UBTOR overexpression suppresses colony formation in cancer cell lines. Studies in cultured cells and zebrafish model show that UBTOR inhibits mTOR signaling by stabilizing the mTOR complex component DEPTOR, and ubtor gene disruption result in higher mTOR activity and aggravate HRAS(G12V) induced neoplasia in the zebrafish. Lastly, UBTOR depletion promotes tumor growth and mTOR signaling in a xenograft mouse model. Together, our results demonstrate how UBTOR regulates cell growth and neoplasia via mTOR signaling. Public Library of Science 2018-08-06 /pmc/articles/PMC6095612/ /pubmed/30080879 http://dx.doi.org/10.1371/journal.pgen.1007583 Text en © 2018 Zhang et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Zhang, Hefei
Zhang, Quan
Gao, Ge
Wang, Xinjian
Wang, Tiantian
Kong, Zhitao
Wang, Guoxiang
Zhang, Cuizhen
Wang, Yun
Peng, Gang
UBTOR/KIAA1024 regulates neurite outgrowth and neoplasia through mTOR signaling
title UBTOR/KIAA1024 regulates neurite outgrowth and neoplasia through mTOR signaling
title_full UBTOR/KIAA1024 regulates neurite outgrowth and neoplasia through mTOR signaling
title_fullStr UBTOR/KIAA1024 regulates neurite outgrowth and neoplasia through mTOR signaling
title_full_unstemmed UBTOR/KIAA1024 regulates neurite outgrowth and neoplasia through mTOR signaling
title_short UBTOR/KIAA1024 regulates neurite outgrowth and neoplasia through mTOR signaling
title_sort ubtor/kiaa1024 regulates neurite outgrowth and neoplasia through mtor signaling
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6095612/
https://www.ncbi.nlm.nih.gov/pubmed/30080879
http://dx.doi.org/10.1371/journal.pgen.1007583
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