TRIM8 modulates STAT3 activity through negative regulation of PIAS3

Okumura, Fumihiro; Matsunaga, Yui; Katayama, Yuta; Nakayama, Keiichi I.; Hatakeyama, Susumi

doi:10.1242/jcs.068981

Cited by 78 publications

(82 citation statements)

References 52 publications

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“…Limited evidence suggests that several of them are oncogenic E3 ligases. For example, SYVN1 has been shown to target p53 and gp78 for degradation (31,32), LPXN may promote prostate cancer metastasis by serving as a co-activator of androgen receptors (33,34), and TRIM8 may promote STAT3 and NF-kB activation (35,36). These candidate E3 ligases warrant further investigation.…”

Section: Discussionmentioning

confidence: 99%

E3 Ubiquitin Ligase RNF126 Promotes Cancer Cell Proliferation by Targeting the Tumor Suppressor p21 for Ubiquitin-Mediated Degradation

et al. 2013

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To identify novel oncogenic E3 ubiquitin ligases as anticancer targets, we screened an E3 ubiquitin ligase siRNA library containing siRNA pools against 555 individual E3s using the sulphorhodamine B assay in the MDA-MB-231 breast cancer cell line and the PC3 prostate cancer cell line. RNF126 was identified and validated as a candidate from this screening. Knockdown of RNF126 dramatically decreased cell viability in these cancer cell lines. Consistently, RNF126 knockdown delayed cell-cycle G 1 -S progression and decreased cell proliferation. Using protein array analysis we found that RNF126 silencing increased cell-cycle dependent kinase inhibitor p21 cip protein levels in both MDA-MB-231 and PC3. Knockdown of RNF126 stabilized the p21 protein rather than increased p21 mRNA levels. We showed that RNF126 interacts with p21 and RNF126 overexpression increased p21 protein ubiquitination in an E3 ligase activity-dependent manner. RNF126 knockdown induced loss of cell viability in MDA-MB-231 and PC-3 can be partially rescued by depletion of p21. RNF126 stable knockdown in PC3 inhibited tumor growth in SCID mice. Finally, we found that RNF126 is highly expressed in a subset of breast cancer cell lines and negatively correlated with p21 expression levels. These findings suggest that RNF126 promotes cancer cell proliferation by targeting p21 for ubiquitin-mediated degradation. RNF126 could be a novel therapeutic target in breast and prostate cancers. Cancer Res; 73(1); 385-94. Ó2012 AACR.

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Section: Discussionmentioning

confidence: 99%

E3 Ubiquitin Ligase RNF126 Promotes Cancer Cell Proliferation by Targeting the Tumor Suppressor p21 for Ubiquitin-Mediated Degradation

et al. 2013

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“…23,48 All these genes were identified as direct targets of miR-17, as evidenced by their significant downregulation upon ectopic miR-17 overexpression. In agreement with these results, miR-17 transfection was also demonstrated to be sufficient to reduce apoptosis induced by serum deprivation in a series of primary UM CLL cells.…”

Section: Discussionmentioning

confidence: 99%

The miR-17∼92 family regulates the response to Toll-like receptor 9 triggering of CLL cells with unmutated IGHV genes

Bomben

Gobessi

et al. 2012

Leukemia

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Chronic lymphocytic leukemia (CLL) cells from clinically aggressive cases have a greater capacity to respond to external microenvironmental stimuli, including those transduced through Toll-like-receptor-9 (TLR9). Concomitant microRNA and gene expression profiling in purified CLL cells (n ¼ 17) expressing either unmutated (UM) or mutated (M) IGHV genes selected microRNAs from the miR-17B92 family as significantly upregulated and in part responsible for modifications in the gene expression profile of UM CLL cells stimulated with the TLR9 agonist CpG. Notably, the stable and sustained upregulation of miR-17B92 microRNAs by CpG was preceded by a transient induction of the proto-oncogene MYC. The enforced expression of miR-17, a major member from this family, reduced the expression of the tumor suppressor genes E2F5, TP53INP1, TRIM8 and ZBTB4, and protected cells from serum-free-induced apoptosis (Pp0.05). Consistently, transfection with miR-17B92 family antagomiRs reduced Bromo-deoxy-uridine incorporation in CpG-stimulated UM CLL cells. Finally, miR-17 expression levels, evaluated in 83 CLL samples, were significantly higher in UM (P ¼ 0.03) and ZAP-70 high (P ¼ 0.02) cases. Altogether, these data reveal a role for microRNAs of the miR-17B92 family in regulating pro-survival and growth-promoting responses of CLL cells to TLR9 triggering. Overall, targeting of this pathway may represent a novel therapeutic option for management of aggressive CLL.

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“…According to the STARS and IPA analysis, the percentage of overrepresented genes at 8°C (blue bars) and 23°C (red bars) is illustrated for BORN (intense colors) and imported rainbow trout (pale colors) suppressor of cytokine signaling 1 (SOCS1) and protein inhibitor of activated STAT3 (PIAS3). Their depletion leads to the activation of cytokine signaling through JAK-STAT activation (Toniato et al 2002;Okumura et al 2010). PELI3 supports the signal transduction through Toll-like receptors (TLRs) to the downstream kinases TRAF6 and IRAK within the Toll-like signaling pathway (Jensen and Whitehead 2003).…”

Section: Protein Degradation Is Highly Regulated At Challengingmentioning

confidence: 99%

Impact of Thermal Stress on Kidney-Specific Gene Expression in Farmed Regional and Imported Rainbow Trout

et al. 2015

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Seasonal water temperatures can be stressful for fish in aquaculture and can therefore negatively influence their welfare. Although the kidney is the crucial organ associated with the primary stress response, knowledge about the stress-modulated kidney transcriptome in salmonids is limited. In the present study, we used a comparative microarray approach to characterize the general gene expression profiles of rainbow trout trunk kidney after a 2-week acclimation to mild heat (23 °C) and cold stress (8 °C). Hypothesizing that local adaptation influences stress performance, we aimed to identify differences in the temperature-induced gene expression in the regional trout strain BORN, in addition to a common imported strain. Moderate temperature challenge provoked typical stress response clusters, including heat-shock proteins or cold-inducible factors, in addition to altered energy metabolism in trout kidney. Mild cold, in particular, enhanced renal protein degradation processes, as well as mRNA and protein synthesis, while it also triggered fatty acid biosynthesis. Mild heat led to cytoskeleton-stabilizing processes and might have facilitated cell damage and infection. Furthermore, both breeding lines used different strategies for energy provision, cellular defense, and cell death/survival pathways. As a main finding, the genes involved in energy provision showed generally higher transcript levels at both temperatures in BORN trout compared to imported trout, indicating adjusted metabolic rates under local environmental conditions. Altogether, this study provides a general overview of stress-induced transcriptional patterns in rainbow trout trunk kidney, in addition to identifying genes and networks that contribute to the robustness of the BORN strain. Our analyses suggest SERPINH1 and CIRBP as general marker genes for heat stress and cold stress in trout, respectively.

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TRIM8 modulates STAT3 activity through negative regulation of PIAS3

Cited by 78 publications

References 52 publications

E3 Ubiquitin Ligase RNF126 Promotes Cancer Cell Proliferation by Targeting the Tumor Suppressor p21 for Ubiquitin-Mediated Degradation

E3 Ubiquitin Ligase RNF126 Promotes Cancer Cell Proliferation by Targeting the Tumor Suppressor p21 for Ubiquitin-Mediated Degradation

The miR-17∼92 family regulates the response to Toll-like receptor 9 triggering of CLL cells with unmutated IGHV genes

Impact of Thermal Stress on Kidney-Specific Gene Expression in Farmed Regional and Imported Rainbow Trout

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