TRIM16 inhibits neuroblastoma cell proliferation through cell cycle regulation and dynamic nuclear localization
| Autor: | Maria Kavallaris, Glenn M. Marshall, A Malyukova, Belamy B. Cheung, Jessica L. Bell |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Tyrosine 3-Monooxygenase
TRIM16 Cellular differentiation proliferation Ubiquitin-Protein Ligases EBBP cyclin D1 Active Transport Cell Nucleus Biology localization Tripartite Motif Proteins Mice Neuroblastoma Cyclin D1 Cell Movement Report Cell Line Tumor medicine cancer Animals Humans RNA Small Interfering Molecular Biology Cell Proliferation Cell Nucleus Cell growth HEK 293 cells G1 Phase p27 Cell Biology Cell cycle medicine.disease G1 Phase Cell Cycle Checkpoints Cell biology DNA-Binding Proteins Cell nucleus medicine.anatomical_structure HEK293 Cells Cancer research cell cycle RNA Interference G1 phase Cyclin-Dependent Kinase Inhibitor p27 Developmental Biology Transcription Factors |
| Zdroj: | Cell Cycle |
| ISSN: | 1551-4005 1538-4101 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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