Characterization of the Oncogenic Activity of the Novel TRIM59 Gene in Mouse Cancer Models
Open Access
- 1 July 2011
- journal article
- Published by American Association for Cancer Research (AACR) in Molecular Cancer Therapeutics
- Vol. 10 (7), 1229-1240
- https://doi.org/10.1158/1535-7163.mct-11-0077
Abstract
A novel TRIM family member, TRIM59 gene was characterized to be upregulated in SV40 Tag oncogene–directed transgenic and knockout mouse prostate cancer models as a signaling pathway effector. We identified two phosphorylated forms of TRIM59 (p53 and p55) and characterized them using purified TRIM59 proteins from mouse prostate cancer models at different stages with wild-type mice and NIH3T3 cells as controls. p53/p55-TRIM59 proteins possibly represent Ser/Thr and Tyr phosphorylation modifications, respectively. Quantitative measurements by ELISA showed that the p-Ser/Thr TRIM59 correlated with tumorigenesis, whereas the p-Tyr-TRIM59 protein correlated with advanced cancer of the prostate (CaP). The function of TRIM59 was elucidated using short hairpin RNA (shRNA)-mediated knockdown of the gene in human CaP cells, which caused S-phase cell-cycle arrest and cell growth retardation. A hit-and-run effect of TRIM59 shRNA knockdown was observed 24 hours posttransfection. Differential cDNA microarrray analysis was conducted, which showed that the initial and rapid knockdown occurred early in the Ras signaling pathway. To confirm the proto-oncogenic function of TRIM59 in the Ras signaling pathway, we generated a transgenic mouse model using a prostate tissue–specific gene (PSP94) to direct the upregulation of the TRIM59 gene. Restricted TRIM59 gene upregulation in the prostate revealed the full potential for inducing tumorigenesis, similar to the expression of SV40 Tag, and coincided with the upregulation of genes specific to the Ras signaling pathway and bridging genes for SV40 Tag–mediated oncogenesis. The finding of a possible novel oncogene in animal models will implicate a novel strategy for diagnosis, prognosis, and therapy for cancer. Mol Cancer Ther; 10(7); 1229–40. ©2011 AACR.Keywords
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This publication has 27 references indexed in Scilit:
- TRIM family proteins and their emerging roles in innate immunityNature Reviews Immunology, 2008
- TRIM21 is an IgG receptor that is structurally, thermodynamically, and kinetically conservedProceedings of the National Academy of Sciences of the United States of America, 2008
- Retrovirus Silencing by an Epigenetic TRIMCell, 2007
- TRIM28 Mediates Primer Binding Site-Targeted Silencing of Murine Leukemia Virus in Embryonic CellsCell, 2007
- The RBCC GeneRFP2(Leu5) Encodes a Novel Transmembrane E3 Ubiquitin Ligase Involved in ERADMolecular Biology of the Cell, 2007
- Structural basis for PRYSPRY-mediated tripartite motif (TRIM) protein functionProceedings of the National Academy of Sciences of the United States of America, 2007
- TRIM25 RING-finger E3 ubiquitin ligase is essential for RIG-I-mediated antiviral activityNature, 2007
- Evolution of a cytoplasmic tripartite motif (TRIM) protein in cows that restricts retroviral infectionProceedings of the National Academy of Sciences of the United States of America, 2006
- Subclassification of the RBCC/TRIM Superfamily Reveals a Novel Motif Necessary for Microtubule BindingJournal of Biological Chemistry, 2006
- Trim5α protein restricts both HIV-1 and murine leukemia virusProceedings of the National Academy of Sciences of the United States of America, 2004