TRIM16 acts as a tumour suppressor by inhibitory effects on cytoplasmic vimentin and nuclear E2F1 in neuroblastoma cells
| Autor: | Eric Sekyere, Anne M. Cunningham, Patrick Y. Kim, A Malyukova, Jessica Koach, Belamy B. Cheung, Jessica L. Bell, Wayne Thomas, Tao Liu, Maria Kavallaris, Murray D. Norris, Vivienne Tobias, Glenn M. Marshall, Michelle Haber, Owen Tan |
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| Rok vydání: | 2010 |
| Předmět: |
Cytoplasm
Cancer Research tumour suppressor Tumor suppressor gene TRIM16 Ubiquitin-Protein Ligases Cellular differentiation EBBP Cell Vimentin Biology medicine.disease_cause Tripartite Motif Proteins Mice Neuroblastoma vimentin Cell Movement Genetics medicine Animals Humans Molecular Biology Cell Nucleus Mice Inbred BALB C Tumor Suppressor Proteins Cell Differentiation Cell cycle medicine.disease DNA-Binding Proteins medicine.anatomical_structure E2F1 Cancer cell biology.protein Cancer research Original Article Female Carcinogenesis E2F1 Transcription Factor Transcription Factors |
| Zdroj: | Oncogene |
| ISSN: | 1476-5594 0950-9232 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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