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

Research output: Contribution to journalArticleResearchpeer-review

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.

LanguageEnglish
Pages6172-6183
Number of pages12
JournalOncogene
Volume29
DOIs
Publication statusPublished - 18 Nov 2010
Externally publishedYes

Fingerprint

Vimentin
Neuroblastoma
Retinoids
Neoplasms
Cell Movement
Down-Regulation
Histone Acetyltransferases
Retinoic Acid Receptors
DNA-Binding Proteins
Cellular Structures
Ganglia
Proteins
Growth

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

Cite this

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. / TRIM16 acts as a tumour suppressor by inhibitory effects on cytoplasmic vimentin and nuclear E2F1 in neuroblastoma cells. In: Oncogene. 2010 ; Vol. 29. pp. 6172-6183.
@article{48948acce2514ee4a5d95f9e85db9468,
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 = "11",
day = "18",
doi = "10.1038/onc.2010.340",
language = "English",
volume = "29",
pages = "6172--6183",
journal = "Oncogene",
issn = "0950-9232",
publisher = "Springer, Springer Nature",

}

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

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

In: Oncogene, Vol. 29, 18.11.2010, p. 6172-6183.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - TRIM16 acts as a tumour suppressor by inhibitory effects on cytoplasmic vimentin and nuclear E2F1 in neuroblastoma cells

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

UR - http://www.scopus.com/inward/record.url?scp=78650196421&partnerID=8YFLogxK

U2 - 10.1038/onc.2010.340

DO - 10.1038/onc.2010.340

M3 - Article

VL - 29

SP - 6172

EP - 6183

JO - Oncogene

T2 - Oncogene

JF - Oncogene

SN - 0950-9232

ER -