The ability of TRIM3 to induce growth arrest depends on RING-dependent E3 ligase activity

Raheja, Radhika; Liu, Yuhui; Hukkelhoven, Ellen; Yeh, Nancy; Koff, Andrew

doi:10.1042/bj20131288

Cited by 36 publications

(38 citation statements)

References 66 publications

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“…Our molecular study revealed that TRIM3 could suppress P53 signaling, facilitate cell growth and resistance to cisplatin-induced cell apoptosis. Our finding indicates TRIM3 plays a oncogenic role in P53 WT breast cancer cells, which is opposite to previous studies [19,31]. This interesting finding not only increases the understanding of P53 post-translational modifications but also implicates the multiface of TRIM3 in different cancer background.…”

Section: Discussioncontrasting

confidence: 97%

“…TRIM3 belongs to the group of tripartite motif family and is composed of zinc-binding domain, RING domain, B1/2 domain and coiled region [31]. TIRM3 was firstly reported as the partner of myosin and facilitate the transportation of the target proteins [18].…”

Section: Discussionmentioning

confidence: 99%

“…TIRM3 was firstly reported as the partner of myosin and facilitate the transportation of the target proteins [18]. TRIM3 were reported to be decreased in several human cancers, such as gastric cancer, colon cancer and liver cancer [19,[31][32][33]. However, although TRIM3 was shown to function as a tumor suppressor gene in several cancer types, we did not observe any dramatic TRIM3 level change in breast cancer compared with normal breast tissue, which might indicated the uncertain role or dual roles of TRIM3 might exist in breast cancer.…”

Section: Discussionmentioning

confidence: 99%

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TRIM3 inhibits P53 signaling in breast cancer cells

Wang

Zhang

Pei

et al. 2020

Preprint

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BackgroundBeast cancer is the most common women cancer worldwide, while two third of them are ER alpha positive breast cancer. Among the ER alpha positive breast cancer, about 80% are P53 wild type, indicating the potential tumor suppression role in ER alpha positive breast cancer. Since P53 is an important safeguard to inhibit cell malignant transformation, reactivating P53 signaling could a plausible approach to treat breast cancer.MethodsTRIM3 protein levels were measured by western blot, while the P53 classical target genes were measured by real-time PCR. WST1 assay were used to measure cell proliferation, while cleaved caspase-3 was used to detect cell apoptosis. Protein stability and ubiquitin assay were used to detect the P53 protein ubiquitin and stability. The immuno-precipitation assays were used to detect the protein interactions. Immuno-staining was used to detect the protein localization of P53 and TRIM3, while the ubiquitin-based immuno-precipitation assays were used to detect the specific ubiquitination manner of P53.ResultsIn our study, we identified TRIM3 as an endogenous inhibitor for P53 signaling. TRIM3 depletion inhibited breast cancer cell proliferation and promoted apoptosis. In addition, TRIM3 depletion increased P53 protein level in breast cancer cell. Further investigation showed that TRIM3 could associate with P53 and promote P53 K48-linked ubiquitination and degradation.ConclusionOur study identified a novel post-translational modification mechanism between TRIM3 and P53. TRIM3 depletion or blockage could be a promising strategy to rescue P53 signaling and inhibit breast cancer progression.Highlights1. TRIM3 facilitates breast cancer cell growth and anti-apotosis.2. TRIM3 inhibits P53 protein and its signaling activity.3. TRIM3 interacts with P53 and promotes P53 K48-linked ubiquitination and degradation.

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Section: Discussioncontrasting

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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TRIM3 inhibits P53 signaling in breast cancer cells

Wang

Zhang

Pei

et al. 2020

Preprint

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“…TRIM3 functions as a tumor suppressor (10–13). Studies of cancer cells have also shown that TRIM3 overexpression can inhibit cell proliferation (13,14). The present results of CCK-8 and western blot (PCNA and cyclin D1) analyses in RA FLS were in accordance with previous findings.…”

Section: Discussionmentioning

confidence: 99%

“…Emerging evidence has suggested that TRIM3 is a candidate tumor suppressor gene for glioblastomas (10–12) and colorectal cancer (13). Overexpression of TRIM3 inhibited cell proliferation of cancer cells (13,14). However, little is known about the expression and function of TRIM proteins, including TRIM3 in RA progression.…”

Section: Introductionmentioning

confidence: 99%

The tripartite motif-containing protein 3 on the proliferation and cytokine secretion of rheumatoid arthritis fibroblast-like synoviocytes

Wang

Guo

et al. 2017

Molecular Medicine Reports

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Recent studies have revealed fibroblast-like synoviocytes (FLS) as a pivotal effector cell in the inflamed joint of rheumatoid arthritis (RA) patients. FLS exhibit high proliferation rates and constitutive expression of cytokines, contributing to the pathogenesis of RA. In this study, we found that the expression of tripartite motif-containing protein 3 (TRIM3), a candidate tumor suppressor gene, was lower in synovial tissue samples of RA patients than in that of healthy controls. We then investigated the role of TRIM3 on the proliferation and cytokine secretion of primary cultured FLS from RA patients. Enforced expression of TRIM3 in RA FLS led to significantly decreased cell proliferation as indicated by Cell Counting Kit-8 assay, reduced secretion of tumor necrosis factor-α (TNF)-α, interleukin (IL)-1β and IL-6 as indicated by enzyme-linked immunosorbent assays, and decreased p38 phosphorylation as assessed by western blot analysis. The proteins promoting cell cycles (cyclin D1 and PCNA) were downregulated and the protein negatively regulating cell cycle progression (p53 and p21) was upregulated after TRIM3 overexpression. Importantly, TRIM3 knockdown had reverse effects on cell proliferation, which was suppressed by the p38-specific inhibitor SB203580. In conclusion, the current results demonstrated the downregulation of TRIM3 expression in RA synovial tissues. Importantly, TRIM3 exerted an anti-proliferation role in RA FLS via p38 signaling pathway.

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Decreased expression of TRIM3 is associated with poor prognosis in patients with primary hepatocellular carcinoma

et al. 2014

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Tripartite motif-containing 3 (TRIM3) is a member of the tripartite motif (TRIM) protein family and is reported to be involved in the pathogenesis of various cancers. The role of TRIM3 in hepatocellular carcinoma (HCC) is unknown; thus, the goal of this study was to explore the expression level and prognostic value of TRIM3 in HCC. The expression level of TRIM3 in HCC surgically resected tumors and corresponding nontumorous samples was detected by real-time quantitative RT-PCR, Western blotting, and immunohistochemistry. The correlation between TRIM3 expression level and the clinicopathological features and prognosis of HCC patients was also analyzed. We observed that TRIM3 expression was remarkably decreased in tumor tissue samples from HCC patients, relative to matched nontumorous tissue samples, at the mRNA (p = 0.018) and protein level (p = 0.02). Similarly, immunohistochemical analysis showed that 53.4 % of samples had low TRIM3 protein expression. Clinicopathological analysis revealed that low TRIM3 expression was significantly correlated with tumor size (p = 0.034), histological grade (p < 0.001), serum AFP (p = 0.025), and TNM stage (p = 0.021). Furthermore, Kaplan-Meier survival analysis revealed that low TRIM3 expression was associated with poor survival in HCC patients. Finally, our multivariate Cox regression analysis showed that TRIM3 expression was an independent prognostic factor for overall survival of HCC patients. In conclusion, this study suggests that TRIM3 may play a significant role in HCC progression and acts as a valuable prognostic marker and potential therapeutic target for HCC.

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The ability of TRIM3 to induce growth arrest depends on RING-dependent E3 ligase activity

Cited by 36 publications

References 66 publications

TRIM3 inhibits P53 signaling in breast cancer cells

TRIM3 inhibits P53 signaling in breast cancer cells

The tripartite motif-containing protein 3 on the proliferation and cytokine secretion of rheumatoid arthritis fibroblast-like synoviocytes

Decreased expression of TRIM3 is associated with poor prognosis in patients with primary hepatocellular carcinoma

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