A novel TRIM family member, Trim69, regulates zebrafish development through p53‐mediated apoptosis

Han, Ruiqin; Zhao, Qing; Zong, Shudong; Miao, Shiying; Song, Wei; Wang, Linfang

doi:10.1002/mrd.22643

Cited by 17 publications

(13 citation statements)

References 30 publications

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“…3). A significant elevation of Bax has been observed in zebrafish embryos with TRIM69 knockdown [26]. Increasing mouse Trim69 expression significantly increases the ratio of Bax-to-Bcl-2 in HEK293 cells [33]; however, our data on the expression of Bcl-2/Bax were inconsistent with those from the above studies, possibly because of species differences.…”

Section: Discussioncontrasting

confidence: 60%

“…Mouse Trim69 co-localizes with promyelocytic leukemia protein and induces HEK293 cell apoptosis [33]. Zebrafish TRIM69 regulates embryo development via down-regulation of the c-Jun and p53 pathways [26,34]. In the present study, we found that the expression of TRIM69 protein was down-regulated in cataract lens anterior capsules (Fig.…”

Section: Discussionsupporting

confidence: 50%

“…TRIM69 is evolutionarily conserved in vertebrates. Knockdown of TRIM69 activates the p53 pathway and increases apoptosis during embryogenesis in zebrafish [26]. Whether TRIM69 plays a role in apoptosis of HLECs and the pathogenesis of cataracts is unclear.…”

Section: Introductionmentioning

confidence: 99%

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TRIM69 inhibits cataractogenesis by negatively regulating p53

Xiao

Rao

et al. 2019

Redox Biology

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Ultraviolet B (UVB) irradiation can induce reactive oxygen species (ROS) production and apoptosis in human lens epithelial cells (HLECs), thus leading to the formation of cataracts. We studied the role of tripartite motif 69 (TRIM69) in cataract formation. The expression of TRIM69 protein was down-regulated in both human cataract capsule tissues and HLECs treated with UVB, whereas the expression of p53 protein exhibited an opposite trend. Ectopic expression of TRIM69 in HLECs significantly suppressed UVB-induced apoptosis and ROS production, whereas knockdown of TRIM69 promoted apoptosis and ROS production. TRIM69 can interact with p53 and induce its ubiquitination. The effects of TRIM69 overexpression in UVB-induced cell apoptosis and ROS production was clearly weakened by p53 overexpression, thus suggesting a role for p53 in TRIM69 functions. Furthermore, inhibition of ROS mitigated the effects of UVB irradiation on ROS production, cell apoptosis, forkhead box protein 3a (Foxo3a) phosphorylation, and TRIM69 expression. Additionally, Foxo3a overexpression significantly enhanced TRIM69 promoter activity, whereas Foxo3a knockdown had the opposite effect. In conclusion, we provide the first demonstration that Foxo3a is a potential transcription factor for TRIM69, and TRIM69 induces p53 ubiquitination. These results suggest that the Foxo3a/TRIM69/p53 regulatory network may be involved in cataract formation.

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Section: Discussioncontrasting

confidence: 60%

Section: Discussionsupporting

confidence: 50%

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TRIM69 inhibits cataractogenesis by negatively regulating p53

Xiao

Rao

et al. 2019

Redox Biology

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“…Here, we identified another TRIM family member, TRIM69 (also known as RNF36, HSD34, and Trif) as an IFN-inducible virus restriction factor. As an E3 ubiquitin ligase [ 45 ], TRIM69 plays crucial roles in apoptosis [ 46 ], tumor control [ 47 ] and zebrafish development [ 48 , 49 ]. However, TRIM69 has not been reported to have any function on antiviral immunity.…”

Section: Introductionmentioning

confidence: 99%

Interferon-stimulated TRIM69 interrupts dengue virus replication by ubiquitinating viral nonstructural protein 3

et al. 2018

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In order to eliminate viral infections, hundreds of interferon-stimulated genes (ISGs) are induced via type I interferons (IFNs). However, the functions and mechanisms of most ISGs are largely unclear. A tripartite motif (TRIM) protein encoding gene TRIM69 is induced by dengue virus (DENV) infection as an ISG. TRIM69 restricts DENV replication, and its RING domain, which has the E3 ubiquitin ligase activity, is critical for its antiviral activity. An in vivo study further confirmed that TRIM69 contributes to the control of DENV infection in immunocompetent mice. Unlike many other TRIM family members, TRIM69 is not involved in modulation of IFN signaling. Instead, TRIM69 interacts with DENV Nonstructural Protein 3 (NS3) directly and mediates its polyubiquitination and degradation. Finally, Lys104 of NS3 is identified as the target of TRIM69-mediated ubiquitination. Our study demonstrates that TRIM69 restricts DENV replication by specifically ubiquitinating a viral nonstructural protein.

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“…The subcellular localization showed that TRIM protein family were located in cytosol and nucleus, and some TRIM proteins are capable to induce apoptosis, while the others, on the contrary, have an inhibitory effect on this process (Nenasheva and Stepanenko, 2018). TRIM69 regulated cell apoptosis through p53 signaling (Han et al, 2016). TRIM31 overexpression promoted K63-linked polyubiquitination of TRAF2 and sustained the activation of NF-kB, which subsequently activated multiple anti-apoptosis downstream genes (Yu et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

Downregulation of miR-3568 Protects Against Ischemia/Reperfusion-Induced Cardiac Dysfunction in Rats and Apoptosis in H9C2 Cardiomyocytes Through Targeting TRIM62

Wang

Liu

et al. 2020

Front. Pharmacol.

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microRNA-3568 (miR-3568) has been reported to be associated with atherosclerosis. Only few data describe the expression and underlying mechanism of miR-3568 in regulating cardiac ischemia-reperfusion (I/R) injury such as apoptosis. In this study, we therefore sought to investigate the potential function of miR-3568 in simulated I/R-induced apoptosis in H9C2 cardiomyocytes and related signaling pathways involved. Flow cytometry was performed to examine the cell apoptosis. The expression of miR-3568, Survivin, Bcl-2, ERK, JNK, p38, AKT, and STAT3 was measured by western blot and quantitative real-time PCR. The correlation between TRIM62 and p-STAT3 was measured by co-immunoprecipitation and ubiquitination. We found that miR-3568 expression in simulated I/R-induced H9C2 cardiomyocytes was increased in a time-dependent manner. miR-3568 mimic transfection in H9C2 cardiomyocytes significantly enhanced cell apoptosis, decreased the expression of Bcl-2 and Survivin, and activated STAT3 signaling, which were reversed by miR-3568 inhibitor. The direct interaction between miR-3568 and the 3′-untranslated region (UTR) of TRIM62 mRNA was confirmed by dualluciferase reporter assay. TRIM62 overexpression or AG490, a selective inhibitor of JAK2/ STAT3 significantly, significantly inhibited I/R and miR-3568 mimic induced cell apoptosis and STAT3 activation. TRIM62 was found to interact with and induce ubiquitination of p-STAT3. The facilitating role of miR-3568 in I/R injury was also observed in our in vivo rat models. In conclusion, our study suggests that miR-3568 promotes simulated I/Rinduced apoptosis in H9C2 cardiomyocytes through targeting TRIM62.

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A novel TRIM family member, Trim69, regulates zebrafish development through p53‐mediated apoptosis

Cited by 17 publications

References 30 publications

TRIM69 inhibits cataractogenesis by negatively regulating p53

TRIM69 inhibits cataractogenesis by negatively regulating p53

Interferon-stimulated TRIM69 interrupts dengue virus replication by ubiquitinating viral nonstructural protein 3

Downregulation of miR-3568 Protects Against Ischemia/Reperfusion-Induced Cardiac Dysfunction in Rats and Apoptosis in H9C2 Cardiomyocytes Through Targeting TRIM62

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