Identification of TRIM22 as a RING finger E3 ubiquitin ligase

Duan, Zhijian; Gao, Bo; Xu, Wei; Xiong, Sidong

doi:10.1016/j.bbrc.2008.07.070

Cited by 60 publications

(75 citation statements)

References 18 publications

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“…We also demonstrated that TRIM22 was a RING finger E3 ubiquitin ligase (4), and its E3 ligase activity was responsible for its antiviral activity against encephalomycocarditis virus as reported by another research group (14). Additionally, several studies indicated that TRIM22 possessed antiretroviral activity depending on certain cell types (15)(16)(17).…”

supporting

confidence: 72%

“…They are characterized by a combination of RING, B-box, and coiled-coil domains (1). The RING domain of many TRIM proteins has been shown to possess E3 ubiquitin ligase activity (2)(3)(4)(5), whereas the B-box and coiledcoil domains may be involved in protein interactions and homo/ heterodimerization (1,2). Recent studies have demonstrated that many members of the TRIM family play important roles in innate antiviral immunity.…”

mentioning

confidence: 99%

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A 5′ Extended IFN-Stimulating Response Element Is Crucial for IFN-γ–Induced Tripartite Motif 22 Expression via Interaction with IFN Regulatory Factor-1

Gao

Wang

et al. 2010

The Journal of Immunology

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Interferon-γ is crucial for the noncytopathic clearance of hepatitis B virus. In our previous study, we demonstrated that an IFN-γ–inducible molecule, tripartite motif (TRIM) 22, played an important role in antiviral immunity against hepatitis B virus. However, the molecular mechanism of TRIM22 induction by IFN-γ is still unclear. In this study, we identified a novel cis-element termed 5′ extended IFN-stimulating response element (5′ eISRE) that was crucial for IFN-γ inducibility of TRIM22 through transfection assays with luciferase reporter constructs and EMSAs. The 5′ eISRE consists of an ISRE-like motif (ACTTTCGTTTCTC) and a 6-bp sequence (AATTTA) upstream of it, and all three thymine triplets of this cis-element (AATTTAACTTTCGTTTCTC) were revealed to contribute to the IFN-γ inducibility of TRIM22 by site-directed mutagenesis. Further studies showed that upon IFN-γ stimulation, the 5′ eISRE could be bound by IFN regulatory factor-1 (IRF-1), but not by STAT1, as demonstrated by supershift analysis and an ELISA-based transcription factor assay. Moreover, overexpression of IRF-1 significantly induced TRIM22 expression, whereas silencing of IRF-1 with specific short interference RNA abolished IFN-γ–induced TRIM22 expression in HepG2 cells, indicating an IRF-1–dependent expression of TRIM22. Taken together, it was demonstrated in this study that a novel cis-element, 5′ eISRE, was crucial for the IFN-γ–induced transcriptional activity of the TRIM22 gene via interaction with IRF-1.

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confidence: 72%

mentioning

confidence: 99%

A 5′ Extended IFN-Stimulating Response Element Is Crucial for IFN-γ–Induced Tripartite Motif 22 Expression via Interaction with IFN Regulatory Factor-1

Gao

Wang

et al. 2010

The Journal of Immunology

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“…As described for other E3 ubiquitin ligases, TRIM22 is ubiquitinated, an event that may be relevant to its regulation. According to our data, pending submission of our manuscript, TRIM22 has been reported to be a novel RING-finger E3 ubiquitin ligase (Duan et al, 2008). In that study, using GST-TRIM22 purified from GST-TRIM22 transfected COS cells as E3 source, the authors found that TRIM22 underwent selfubiquitination in combination with the E2 enzyme UbcH5b, in an in vitro ubiquitination assay.…”

Section: Discussionmentioning

confidence: 87%

“…In addition, the existence of other unidentified E3 ligases targeting 3C PRO ubiquitina- tion can not be excluded. Duan et al (2008) reported that TRIM22 E3 ligase activity was dependent on UbcH5b as an E2 partner. Because UbcH5a and UbcH5b are functionally homologous, we can hypothesize that the unknown E3 ligase may be TRIM22.…”

Section: Discussionmentioning

confidence: 99%

TRIM22 E3 ubiquitin ligase activity is required to mediate antiviral activity against encephalomyocarditis virus

Eldin

Papon

Oteiza

et al. 2009

Journal of General Virology

108

109

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The interferon (IFN) system is a major effector of the innate immunity that allows time for the subsequent establishment of an adaptive immune response against a wide-range of pathogens. Their diverse biological actions are thought to be mediated by the products of specific but usually overlapping sets of cellular genes induced in the target cells. Ubiquitin ligase members of the tripartite motif (TRIM) protein family have emerged as IFN-induced proteins involved in both innate and adaptive immunity. In this report, we provide evidence that TRIM22 is a functional E3 ubiquitin ligase that is also ubiquitinated itself. We demonstrate that TRIM22 expression leads to a viral protection of HeLa cells against encephalomyocarditis virus infections. This effect is dependent upon its E3 ubiquitinating activity, since no antiviral effect was observed in cells expressing a TRIM22-deletion mutant defective in ubiquitinating activity. Consistent with this, TRIM22 interacts with the viral 3C protease (3C PRO ) and mediates its ubiquitination. Altogether, our findings demonstrate that TRIM22 E3 ubiquitin ligase activity represents a new antiviral pathway induced by IFN against picornaviruses. INTRODUCTIONPicornaviruses include important human pathogens such as rhinovirus, poliovirus and hepatitis A virus, as well as significant insect, plant and agricultural pathogens, such as foot-and-mouth disease virus (Whitton et al., 2005). Encephalomyocarditis virus (EMCV) is the prototype of the cardiovirus subgroup of picornaviruses. Its genome consists of a single-strand of messenger-sense RNA. Viral proteins are expressed from a large open reading frame encoding a giant precursor polyprotein (approx. 255 kDa), which is processed through a series of proteolytic cleavages to produce both capsid and non-structural proteins (Palmenberg, 1990). The majority of the processing reactions are carried out by the 3C protease (3C PRO ), which acts both inter-and intramolecularly to produce polyprotein precursors as well as the mature 3C PRO polypeptide (Palmenberg et al., 1979). Cleavage of the polyprotein normally occurs between glutamine-glycine or glutamine-serine amino acid pairs, which are usually flanked by proline residues (Palmenberg et al., 1984). Besides its commitment to the processing of the viral polyprotein, picornaviral 3C PRO can also facilitate virus replication by altering fundamental cellular processes such as transcription and translation of host cell mRNA (Barral et al., 2007;Ehrenfeld, 1982;Kuyumcu-Martinez et al., 2004; Neznanov et al., 2005;Shen et al., 1996;Yalamanchili et al., 1996Yalamanchili et al., , 1997. Because the regulated proteolysis mediated by 3C PRO is a critical feature in both the processing of picornaviral polyprotein and the inhibition of cellular defences, 3C PRO constitutes an important target for host antiviral innate pathways. Consistent with this, the degradation of EMCV 3C PRO by the ubiquitin/26S proteasome system has been reported (Losick et al., 2003;Schlax et al., 2007). Although the precise ro...

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“…19,22,23 Moreover, in the serum-starved U2OS cell line, TRIM22 was localized in both the nucleus and cytoplasm. 19,24,25 Gao and colleagues observed that TRIM22 was mainly localized in the nucleus of HepG2 cells when it suppresses HBV survival.…”

Section: Ifn-a-induced Trim22 Interrupts Hcv Replicationmentioning

confidence: 97%

Interferon alpha (IFNα)-induced TRIM22 interrupts HCV replication by ubiquitinating NS5A

et al. 2015

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TRIM22, a tripartite-motif (TRIM) protein, is upregulated upon interferon alpha (IFNa) administration to hepatitis C virus (HCV)-infected patients. However, the physiological role of TRIM22 upregulation remains unclear. Here, we describe a potential antiviral function of TRIM22's targeting of the HCV NS5A protein. NS5A is important for HCV replication and for resistance to IFNa therapy. During the first 24 h following the initiation of IFNa treatment, upregulation of TRIM22 in the peripheral blood mononuclear cells (PBMCs) of HCV patients correlated with a decrease in viral titer. This phenomenon was confirmed in the hepatocyte-derived cell line Huh-7, which is highly permissive for HCV infection. TRIM22 over-expression inhibited HCV replication, and Small interfering RNA (siRNA)-mediated knockdown of TRIM22 diminished IFNa-induced anti-HCV function. Furthermore, we determined that TRIM22 ubiquitinates NS5A in a concentration-dependent manner. In summary, our results suggest that TRIM22 upregulation is associated with HCV decline during IFNa treatment and plays an important role in controlling HCV replication in vitro.

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Identification of TRIM22 as a RING finger E3 ubiquitin ligase

Cited by 60 publications

References 18 publications

A 5′ Extended IFN-Stimulating Response Element Is Crucial for IFN-γ–Induced Tripartite Motif 22 Expression via Interaction with IFN Regulatory Factor-1

A 5′ Extended IFN-Stimulating Response Element Is Crucial for IFN-γ–Induced Tripartite Motif 22 Expression via Interaction with IFN Regulatory Factor-1

TRIM22 E3 ubiquitin ligase activity is required to mediate antiviral activity against encephalomyocarditis virus

Interferon alpha (IFNα)-induced TRIM22 interrupts HCV replication by ubiquitinating NS5A

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