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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...

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Autores principales: Bell, Jessica L., Malyukova, Alena, Kavallaris, Maria, Marshall, Glenn M., Cheung, Belamy B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Landes Bioscience 2013
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.
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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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