TRIM26 Maintains Cell Survival in Response to Oxidative Stress through Regulating DNA Glycosylase Stability

Konis, Sifaddin M. R.; Hughes, Jonathan; Parsons, Jason L.

doi:10.3390/ijms231911613

Cited by 3 publications

(3 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Protein stability is mainly controlled by the ubiquitination system. As TRIM26 is known to assemble several different types of ubiquitin chains [ 12 , 14 , 23 ], we wondered whether TRIM26 plays a role in GPX4 ubiquitination. To test this, we overexpressed Myc-GPX4 and Flag-TRIM26 with HA-Ub WT, HA-Ub K48 (with other K residues mutated into R except K48), or HA-Ub K48R (with K48 residues mutated into R) in HEK293T cells and conducted denaturing-IP (d-IP) assays.…”

Section: Resultsmentioning

confidence: 99%

“…TRIM26 is a member of the tripartite motif (TRIM) family proteins [ 9 ], possessing a conserved structural arrangement of the RING domain, the B-box domain and the coiled-coil motif at the N-terminus [ 10 ], which is involved in multiple biological processes, including innate immunity [ 11 ], cell proliferation [ 12 ], and the inflammatory response [ 13 ]. As an E3 ligase, TRIM26 was reported to catalyze ubiquitination of its target proteins, such as TAF7 [ 14 ], TAB1 [ 13 ], ZEB1 [ 12 ], SOX2 [ 15 ] and PBX1 [ 16 ]. Dysregulation of TRIM26 has been implicated in several cancers including glioma [ 15 ], but the molecular mechanisms governing its activation remain to be explored.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The E3 ligase TRIM26 suppresses ferroptosis through catalyzing K63-linked ubiquitination of GPX4 in glioma

Wang,

Xia,

Wang

et al. 2023

Cell Death Dis

View full text Add to dashboard Cite

The selenium-containing enzyme GPX4 moonlights as a central regulator of ferroptosis, an iron-dependent, nonapoptotic form of regulated cell death caused by lipid peroxidation. Yet, little is known about the mechanisms underlying the regulation of its post-transcriptional modifications. Here, we identify the tripartite motif-containing protein TRIM26 as an E3 ubiquitin ligase of GPX4. TRIM26 directly interacts with GPX4 through its Ring domain and catalyzes the ubiquitination of GPX4 at K107 and K117, which promotes the switch in polyubiquitination of GPX4 from K48 to K63, thus enhancing GPX4 protein stability. Moreover, PLK1-mediated S127 phosphorylation of TRIM26 enhances the interaction between TRIM26 and GPX4. Inhibition of TRIM26 phosphorylation causes a reduction in GPX4 K63-linked polyubiquitination and diminishes GPX4 protein levels in tumor cells. Further investigation revealed that TRIM26 is overexpressed in glioma cells. TRIM26 silencing dramatically impedes ferroptosis resistance and tumorigenesis in glioma in vivo and in vitro. Clinically, TRIM26 expression shows a direct correlation with GPX4 and PLK1 levels in glioma samples and is associated with poor outcome in patients with glioma. Collectively, these findings define the role of GPX4 K63-linked polyubiquitination in ferroptosis and suggest a potential strategy for glioma treatment.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The E3 ligase TRIM26 suppresses ferroptosis through catalyzing K63-linked ubiquitination of GPX4 in glioma

Wang,

Xia,

Wang

et al. 2023

Cell Death Dis

View full text Add to dashboard Cite

show abstract

“…TRIM26 KD was carried out by transfection of siRNA for TRIM26 (siTRIM26: Santa Cruz Biotechnology, TX, USA, or siTRIM26#2: 5’- CCGGAGAAUUCUCAGAUAA -3′ 39 ). Negative control #1 siRNA (Thermo Fisher Scientific) was used as the negative control siRNA (siNC).…”

Section: Methodsmentioning

confidence: 99%

TRIM26 positively affects hepatitis B virus replication by inhibiting proteasome-dependent degradation of viral core protein

Nakaya,

Nishizawa,

Nishitsuji

et al. 2023

Sci Rep

View full text Add to dashboard Cite

Chronic hepatitis B virus (HBV) infection is a major medical concern worldwide. Current treatments for HBV infection effectively inhibit virus replication; however, these treatments cannot cure HBV and novel treatment-strategies should be necessary. In this study, we identified tripartite motif-containing protein 26 (TRIM26) could be a supportive factor for HBV replication. Small interfering RNA-mediated TRIM26 knockdown (KD) modestly attenuated HBV replication in human hepatocytes. Endogenous TRIM26 physically interacted with HBV core protein (HBc), but not polymerase and HBx, through the TRIM26 SPRY domain. Unexpectedly, TRIM26 inhibited HBc ubiquitination even though TRIM26 is an E3 ligase. HBc was degraded by TRIM26 KD in Huh-7 cells, whereas the reduction was restored by a proteasome inhibitor. RING domain-deleted TRIM26 mutant (TRIM26ΔR), a dominant negative form of TRIM26, sequestered TRIM26 from HBc, resulting in promoting HBc degradation. Taking together, this study demonstrated that HBV utilizes TRIM26 to avoid the proteasome-dependent HBc degradation. The interaction between TRIM26 and HBc might be a novel therapeutic target against HBV infection.

show abstract

TRIM26 inhibited osteosarcoma progression through destabilizing RACK1 and thus inactivation of MEK/ERK signaling

Xia,

Zheng,

Wei

et al. 2023

Cell Death Dis

View full text Add to dashboard Cite

Osteosarcoma is a highly aggressive malignant tumor that is common in the pediatric population and has a high rate of disability and mortality. Recent studies have suggested that the tripartite motif-containing family genes (TRIMs) play critical roles in oncogenesis in several cancers. TRIM26, one of the TRIMs family genes, was more frequently reported to exert a tumor-suppressive role, while its detailed functional roles in the osteosarcoma progression were still unknown and require further investigation. Herein, we found that TRIM26 was markedly downregulated in osteosarcoma tissues and cells. Survival analysis revealed that higher expression of TRIM26 was associated with better prognosis and its expression was an independent protective factor in osteosarcoma. Functional analysis demonstrated that overexpression of TRIM26 inhibited osteosarcoma cell proliferation and invasion via inhibiting the EMT process and MEK/ERK signaling. In contrast, the silence of TRIM26 caused the opposite effect. RACK1, a member of the Trp-Asp repeat protein family, was identified as a novel target of TRIM26. TRIM26 could interact with RACK1 and accelerate the degradation of RACK1, thus inactivation of MEK/ERK signaling. Overexpression of RACK1 could attenuate the inhibitory effect of TRIM26 overexpression on p-MEK1/2 and p-ERK1/2, and silence of RACK1 could partly impair the effect of TRIM26 knockdown-induced upregulation of p-MEK1/2 and p-ERK1/2. Further, a series of gain- and loss-of-function experiments showed that decreased malignant behaviors including cell proliferation and invasion in TRIM26-upregulated cells were reversed when RACK1 was overexpressed, whereas RACK1 knockdown diminished the increased malignant phenotypes in TRIM26-silenced osteosarcoma cells. In conclusion, our study indicated that TRIM26 inhibited osteosarcoma progression via promoting proteasomal degradation of RACK1, thereby resulting in inactivation of MEK/ERK signaling, and impeding the EMT process.

show abstract

TRIM26 Maintains Cell Survival in Response to Oxidative Stress through Regulating DNA Glycosylase Stability

Cited by 3 publications

References 54 publications

The E3 ligase TRIM26 suppresses ferroptosis through catalyzing K63-linked ubiquitination of GPX4 in glioma

The E3 ligase TRIM26 suppresses ferroptosis through catalyzing K63-linked ubiquitination of GPX4 in glioma

TRIM26 positively affects hepatitis B virus replication by inhibiting proteasome-dependent degradation of viral core protein

TRIM26 inhibited osteosarcoma progression through destabilizing RACK1 and thus inactivation of MEK/ERK signaling

Contact Info

Product

Resources

About