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TRIM16 inhibits neuroblastoma cell proliferation through cell cycle regulation and dynamic nuclear localization
Neuroblastoma is the most common solid tumor in childhood and represents 15% of all children’s cancer deaths. We have previously demonstrated that tripartite motif 16 (TRIM16), a member of the RING B-box coiled-coil (RBCC)/tripartite totif (TRIM) protein family, has significant effects on neuroblast...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Landes Bioscience
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3637347/ https://www.ncbi.nlm.nih.gov/pubmed/23422002 http://dx.doi.org/10.4161/cc.23825 |
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author | Bell, Jessica L. Malyukova, Alena Kavallaris, Maria Marshall, Glenn M. Cheung, Belamy B. |
author_facet | Bell, Jessica L. Malyukova, Alena Kavallaris, Maria Marshall, Glenn M. Cheung, Belamy B. |
author_sort | Bell, Jessica L. |
collection | PubMed |
description | Neuroblastoma is the most common solid tumor in childhood and represents 15% of all children’s cancer deaths. We have previously demonstrated that tripartite motif 16 (TRIM16), a member of the RING B-box coiled-coil (RBCC)/tripartite totif (TRIM) protein family, has significant effects on neuroblastoma proliferation and migration in vitro and tumorigenicity in vivo. However, the mechanism by which this putative tumor suppressor influences cell proliferation and tumorigenicity was undetermined. Here we show, for the first time, TRIM16’s striking pattern of expression and dynamic localization during cell cycle progression and neuroblastoma tumor development. In a tyrosine hydroxylase MYCN (TH-MYCN) neuroblastoma mouse model, immunohistochemical staining revealed strong nuclear TRIM16 expression in differentiating ganglia cells but not in the tumor-initiating cells. Furthermore in vitro studies clearly demonstrated that during G(1) cell cycle phase, TRIM16 protein expression is upregulated and shifts to the nucleus of cells. TRIM16 also plays a role in cell cycle progression through changes in Cyclin D1 and p27 expression. Importantly, using TRIM16 deletion mutants, an uncharacterized protein domain of TRIM16 was found to be required for both TRIM16’s growth inhibitory effects and its nuclear localization. Taken together, our data suggest that TRIM16 acts as a novel regulator of both neuroblastoma G(1)/S progression and cell differentiation. |
format | Online Article Text |
id | pubmed-3637347 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Landes Bioscience |
record_format | MEDLINE/PubMed |
spelling | pubmed-36373472013-04-29 TRIM16 inhibits neuroblastoma cell proliferation through cell cycle regulation and dynamic nuclear localization Bell, Jessica L. Malyukova, Alena Kavallaris, Maria Marshall, Glenn M. Cheung, Belamy B. Cell Cycle Report Neuroblastoma is the most common solid tumor in childhood and represents 15% of all children’s cancer deaths. We have previously demonstrated that tripartite motif 16 (TRIM16), a member of the RING B-box coiled-coil (RBCC)/tripartite totif (TRIM) protein family, has significant effects on neuroblastoma proliferation and migration in vitro and tumorigenicity in vivo. However, the mechanism by which this putative tumor suppressor influences cell proliferation and tumorigenicity was undetermined. Here we show, for the first time, TRIM16’s striking pattern of expression and dynamic localization during cell cycle progression and neuroblastoma tumor development. In a tyrosine hydroxylase MYCN (TH-MYCN) neuroblastoma mouse model, immunohistochemical staining revealed strong nuclear TRIM16 expression in differentiating ganglia cells but not in the tumor-initiating cells. Furthermore in vitro studies clearly demonstrated that during G(1) cell cycle phase, TRIM16 protein expression is upregulated and shifts to the nucleus of cells. TRIM16 also plays a role in cell cycle progression through changes in Cyclin D1 and p27 expression. Importantly, using TRIM16 deletion mutants, an uncharacterized protein domain of TRIM16 was found to be required for both TRIM16’s growth inhibitory effects and its nuclear localization. Taken together, our data suggest that TRIM16 acts as a novel regulator of both neuroblastoma G(1)/S progression and cell differentiation. Landes Bioscience 2013-03-15 2013-02-19 /pmc/articles/PMC3637347/ /pubmed/23422002 http://dx.doi.org/10.4161/cc.23825 Text en Copyright © 2013 Landes Bioscience http://creativecommons.org/licenses/by-nc/3.0/ This is an open-access article licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License. The article may be redistributed, reproduced, and reused for non-commercial purposes, provided the original source is properly cited. |
spellingShingle | Report Bell, Jessica L. Malyukova, Alena Kavallaris, Maria Marshall, Glenn M. Cheung, Belamy B. TRIM16 inhibits neuroblastoma cell proliferation through cell cycle regulation and dynamic nuclear localization |
title | TRIM16 inhibits neuroblastoma cell proliferation through cell cycle regulation and dynamic nuclear localization |
title_full | TRIM16 inhibits neuroblastoma cell proliferation through cell cycle regulation and dynamic nuclear localization |
title_fullStr | TRIM16 inhibits neuroblastoma cell proliferation through cell cycle regulation and dynamic nuclear localization |
title_full_unstemmed | TRIM16 inhibits neuroblastoma cell proliferation through cell cycle regulation and dynamic nuclear localization |
title_short | TRIM16 inhibits neuroblastoma cell proliferation through cell cycle regulation and dynamic nuclear localization |
title_sort | trim16 inhibits neuroblastoma cell proliferation through cell cycle regulation and dynamic nuclear localization |
topic | Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3637347/ https://www.ncbi.nlm.nih.gov/pubmed/23422002 http://dx.doi.org/10.4161/cc.23825 |
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