TRIM16 acts as a tumour suppressor by inhibitory effects on cytoplasmic vimentin and nuclear E2F1 in neuroblastoma cells

G. M. Marshall; J. L. Bell; J. Koach; O. Tan; P. Kim; A. Malyukova; W. Thomas; E. O. Sekyere; T. Liu; A. M. Cunningham; V. Tobias; M. D. Norris; M. Haber; M. Kavallaris; B. B. Cheung

doi:10.1038/onc.2010.340

TRIM16 acts as a tumour suppressor by inhibitory effects on cytoplasmic vimentin and nuclear E2F1 in neuroblastoma cells

G. M. Marshall, J. L. Bell, J. Koach, O. Tan, P. Kim, A. Malyukova, W. Thomas, E. O. Sekyere, T. Liu, A. M. Cunningham, V. Tobias, M. D. Norris, M. Haber, M. Kavallaris, B. B. Cheung

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Abstract

The family of tripartite-motif (TRIM) proteins are involved in diverse cellular processes, but are often characterized by critical protein-protein interactions necessary for their function. TRIM16 is induced in different cancer types, when the cancer cell is forced to proceed down a differentiation pathway. We have identified TRIM16 as a DNA-binding protein with histone acetylase activity, which is required for the retinoic acid receptor Β 2 transcriptional response in retinoid-treated cancer cells. In this study, we show that overexpressed TRIM16 reduced neuroblastoma cell growth, enhanced retinoid-induced differentiation and reduced tumourigenicity in vivo. TRIM16 was only expressed in the differentiated ganglion cell component of primary human neuroblastoma tumour tissues. TRIM16 bound directly to cytoplasmic vimentin and nuclear E2F1 in neuroblastoma cells. TRIM16 reduced cell motility and this required downregulation of vimentin. Retinoid treatment and enforced overexpression caused TRIM16 to translocate to the nucleus, and bind to and downregulate nuclear E2F1, required for cell replication. This study, for the first time, demonstrates that TRIM16 acts as a tumour suppressor, affecting neuritic differentiation, cell migration and replication through interactions with cytoplasmic vimentin and nuclear E2F1 in neuroblastoma cells.

Original language	English
Pages (from-to)	6172-6183
Number of pages	12
Journal	Oncogene
Volume	29
DOIs	https://doi.org/10.1038/onc.2010.340
Publication status	Published - 18 Nov 2010
Externally published	Yes

Bibliographical note

Copyright the Publisher 2010. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

Keywords

TRIM16
EBBP
neuroblastoma
vimentin
E2F1
tumour suppressor

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Publisher version (open access)Final published version, 1.11 MBLicence: CC BY-NC-ND

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Marshall, G. M., Bell, J. L., Koach, J., Tan, O., Kim, P., Malyukova, A., Thomas, W., Sekyere, E. O., Liu, T., Cunningham, A. M., Tobias, V., Norris, M. D., Haber, M., Kavallaris, M., & Cheung, B. B. (2010). TRIM16 acts as a tumour suppressor by inhibitory effects on cytoplasmic vimentin and nuclear E2F1 in neuroblastoma cells. Oncogene, 29, 6172-6183. https://doi.org/10.1038/onc.2010.340

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title = "TRIM16 acts as a tumour suppressor by inhibitory effects on cytoplasmic vimentin and nuclear E2F1 in neuroblastoma cells",

abstract = "The family of tripartite-motif (TRIM) proteins are involved in diverse cellular processes, but are often characterized by critical protein-protein interactions necessary for their function. TRIM16 is induced in different cancer types, when the cancer cell is forced to proceed down a differentiation pathway. We have identified TRIM16 as a DNA-binding protein with histone acetylase activity, which is required for the retinoic acid receptor Β 2 transcriptional response in retinoid-treated cancer cells. In this study, we show that overexpressed TRIM16 reduced neuroblastoma cell growth, enhanced retinoid-induced differentiation and reduced tumourigenicity in vivo. TRIM16 was only expressed in the differentiated ganglion cell component of primary human neuroblastoma tumour tissues. TRIM16 bound directly to cytoplasmic vimentin and nuclear E2F1 in neuroblastoma cells. TRIM16 reduced cell motility and this required downregulation of vimentin. Retinoid treatment and enforced overexpression caused TRIM16 to translocate to the nucleus, and bind to and downregulate nuclear E2F1, required for cell replication. This study, for the first time, demonstrates that TRIM16 acts as a tumour suppressor, affecting neuritic differentiation, cell migration and replication through interactions with cytoplasmic vimentin and nuclear E2F1 in neuroblastoma cells.",

keywords = "TRIM16, EBBP, neuroblastoma, vimentin, E2F1, tumour suppressor",

author = "Marshall, {G. M.} and Bell, {J. L.} and J. Koach and O. Tan and P. Kim and A. Malyukova and W. Thomas and Sekyere, {E. O.} and T. Liu and Cunningham, {A. M.} and V. Tobias and Norris, {M. D.} and M. Haber and M. Kavallaris and Cheung, {B. B.}",

note = "Copyright the Publisher 2010. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher. ",

year = "2010",

month = nov,

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doi = "10.1038/onc.2010.340",

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Marshall, GM, Bell, JL, Koach, J, Tan, O, Kim, P, Malyukova, A, Thomas, W, Sekyere, EO, Liu, T, Cunningham, AM, Tobias, V, Norris, MD, Haber, M, Kavallaris, M & Cheung, BB 2010, 'TRIM16 acts as a tumour suppressor by inhibitory effects on cytoplasmic vimentin and nuclear E2F1 in neuroblastoma cells', Oncogene, vol. 29, pp. 6172-6183. https://doi.org/10.1038/onc.2010.340

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AU - Marshall, G. M.

AU - Bell, J. L.

AU - Koach, J.

AU - Tan, O.

AU - Kim, P.

AU - Malyukova, A.

AU - Thomas, W.

AU - Sekyere, E. O.

AU - Liu, T.

AU - Cunningham, A. M.

AU - Tobias, V.

AU - Norris, M. D.

AU - Haber, M.

AU - Kavallaris, M.

AU - Cheung, B. B.

N1 - Copyright the Publisher 2010. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

PY - 2010/11/18

Y1 - 2010/11/18

N2 - The family of tripartite-motif (TRIM) proteins are involved in diverse cellular processes, but are often characterized by critical protein-protein interactions necessary for their function. TRIM16 is induced in different cancer types, when the cancer cell is forced to proceed down a differentiation pathway. We have identified TRIM16 as a DNA-binding protein with histone acetylase activity, which is required for the retinoic acid receptor Β 2 transcriptional response in retinoid-treated cancer cells. In this study, we show that overexpressed TRIM16 reduced neuroblastoma cell growth, enhanced retinoid-induced differentiation and reduced tumourigenicity in vivo. TRIM16 was only expressed in the differentiated ganglion cell component of primary human neuroblastoma tumour tissues. TRIM16 bound directly to cytoplasmic vimentin and nuclear E2F1 in neuroblastoma cells. TRIM16 reduced cell motility and this required downregulation of vimentin. Retinoid treatment and enforced overexpression caused TRIM16 to translocate to the nucleus, and bind to and downregulate nuclear E2F1, required for cell replication. This study, for the first time, demonstrates that TRIM16 acts as a tumour suppressor, affecting neuritic differentiation, cell migration and replication through interactions with cytoplasmic vimentin and nuclear E2F1 in neuroblastoma cells.

AB - The family of tripartite-motif (TRIM) proteins are involved in diverse cellular processes, but are often characterized by critical protein-protein interactions necessary for their function. TRIM16 is induced in different cancer types, when the cancer cell is forced to proceed down a differentiation pathway. We have identified TRIM16 as a DNA-binding protein with histone acetylase activity, which is required for the retinoic acid receptor Β 2 transcriptional response in retinoid-treated cancer cells. In this study, we show that overexpressed TRIM16 reduced neuroblastoma cell growth, enhanced retinoid-induced differentiation and reduced tumourigenicity in vivo. TRIM16 was only expressed in the differentiated ganglion cell component of primary human neuroblastoma tumour tissues. TRIM16 bound directly to cytoplasmic vimentin and nuclear E2F1 in neuroblastoma cells. TRIM16 reduced cell motility and this required downregulation of vimentin. Retinoid treatment and enforced overexpression caused TRIM16 to translocate to the nucleus, and bind to and downregulate nuclear E2F1, required for cell replication. This study, for the first time, demonstrates that TRIM16 acts as a tumour suppressor, affecting neuritic differentiation, cell migration and replication through interactions with cytoplasmic vimentin and nuclear E2F1 in neuroblastoma cells.

KW - TRIM16

KW - EBBP

KW - neuroblastoma

KW - vimentin

KW - E2F1

KW - tumour suppressor

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DO - 10.1038/onc.2010.340

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AN - SCOPUS:78650196421

SN - 0950-9232

VL - 29

SP - 6172

EP - 6183

JO - Oncogene

JF - Oncogene

ER -

TRIM16 acts as a tumour suppressor by inhibitory effects on cytoplasmic vimentin and nuclear E2F1 in neuroblastoma cells

Abstract

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Keywords

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