Negative Regulation of Interferon-induced Transmembrane Protein 3 by SET7-mediated Lysine Monomethylation

Zhao, Shuyuan; Han, Qun; Nie, Jia; Cao, Xuezhi; Chen, Zuojia; Yin, Shuying; Gao, Yayi; Lin, Fang; Zhou, Xiaohui; Xu, Ke; Fan, Huimin; Zhou, Qian; Sun, Bing; Zhong, Jin; Li, Bin; Tsun, Andy

doi:10.1074/jbc.m113.511949

Cited by 45 publications

(52 citation statements)

References 32 publications

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“…Additionally, Set7 was recently found to promote HIV transcription via monomethylated Tat protein (28). Recent studies showed that the antiviral function of IFN-induced transmembrane 3 protein for vesicular stomatitis virus and influenza A virus could be attenuated by Set7 (29). Taken together, these findings suggested that Set7 may play a role in virus infection or replication.…”

Section: H Epatitis C Virus (Hcv) Was First Discovered As Non-a Non-supporting

confidence: 51%

Set7 Facilitates Hepatitis C Virus Replication via Enzymatic Activity–Dependent Attenuation of the IFN-Related Pathway

Han

Wang

Zhao

et al. 2015

The Journal of Immunology

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Hepatitis C virus (HCV) infection is a major cause of chronic liver disease, usually resulting in persistent infection involving hepatic steatosis, cirrhosis, and hepatocellular carcinoma via escape of the host’s immune response. Set7 is a lysine-specific methyltransferase that is involved in gene regulation and virus replication. However, the mechanism underlying the immune evasion between HCV and Set7 is not well understood. In this study, we observed that the expression of Set7 in Huh7.5.1 cells was upregulated by HCV infection, and high levels of Set7 expression were also found in the sera, PBMCs, and liver tissue of HCV patients relative to healthy individuals. Further investigation showed that Set7 enhanced HCV replication in an enzymatic activity–dependent manner. Moreover, our data showed that Set7 decreased the expression of virus-induced IFN and IFN-related effectors, such as dsRNA-activated protein kinase and 2′,5′-oligoadenylate synthetase. Further investigation suggested that Set7 suppressed the endogenous IFN expression by reducing the nuclear translocation of IFN regulatory factor 3/7 and the p65 subunit of NF-κB and reduced IFN-induced dsRNA-activated protein kinase and 2′,5′-oligoadenylate synthetase via attenuation of the phosphorylation of STAT1 and STAT2. Additionally, IFN receptors, including IFNAR1 and IFNAR2, which are located upstream of the JAK/STAT pathway, were reduced by Set7. Taken together, our results reveal that Set7 facilitates HCV replication through the attenuation of IFN signaling pathways and IFN-related effectors.

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Section: H Epatitis C Virus (Hcv) Was First Discovered As Non-a Non-supporting

confidence: 51%

Set7 Facilitates Hepatitis C Virus Replication via Enzymatic Activity–Dependent Attenuation of the IFN-Related Pathway

Han

Wang

Zhao

et al. 2015

The Journal of Immunology

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“…The posttranslational regulation of IFITM3 is rich with complexity. At least eight distinct amino acids within this small, 15-kDa protein are modified with at least four different posttranslational modifications, including phosphorylation, palmitoylation, ubiquitination, and methylation (4,19,22,23). We .…”

Section: Discussionmentioning

confidence: 99%

“…This modification negatively regulates IFITM3 by targeting the protein away from endolysosomes for degradation (4). Set7-dependent methylation on a single lysine has also been described to negatively regulate IFITM3 antiviral activity through an unknown mechanism (22). Finally, IFITM3 phosphorylation by the protein-tyrosine kinase FYN on tyrosine 20 (Tyr 20 ) has been reported (23).…”

Section: Interferon-inducible Transmembrane Protein 3 (Ifitm3) Is Essmentioning

confidence: 99%

Phosphorylation of the Antiviral Protein Interferon-inducible Transmembrane Protein 3 (IFITM3) Dually Regulates Its Endocytosis and Ubiquitination

Chesarino¹,

McMichael

Hach

et al. 2014

Journal of Biological Chemistry

126

186

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“…So far, we have presented several examples of how SETD7 can directly influence chromatin and transcription, but SETD7 also methylates proteins in the cytoplasm that are important for various cellular responses and pathways. SETD7 methylates Yes-associated protein (YAP), a Hippo pathway transducer to promote its cytoplasmic retention [35], as well as the interferon-induced transmembrane protein 3 (IFITM3) to reduce its antiviral activity [36]. Other non-histone substrates of SETD7 include AKA6, CENPC1, MeCP2, MINT, PPARBP, ZDH8, Cullin 1, IRF1, and TTK, all of which were identified by a peptide array methylation-based analysis [15]; however, the biological functions of these methylation events remain to be determined.…”

Section: Setd7mentioning

confidence: 99%

Emerging roles of lysine methylation on non-histone proteins

Zhang

Huang

Shi

2015

Cell. Mol. Life Sci.

121

103

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Lysine methylation is a common posttranslational modification (PTM) of histones that is important for the epigenetic regulation of transcription and chromatin in eukaryotes. Increasing evidence demonstrates that in addition to histones, lysine methylation also occurs on various non-histone proteins, especially transcription- and chromatin-regulating proteins. In this review, we will briefly describe the histone lysine methyltransferases (KMTs) that have a broad spectrum of non-histone substrates. We will use p53 and nuclear receptors, especially estrogen receptor alpha, as examples to discuss the dynamic nature of non-histone protein lysine methylation, the writers, erasers, and readers of these modifications, and the crosstalk between lysine methylation and other PTMs in regulating the functions of the modified proteins. Understanding the roles of lysine methylation in normal cells and during development will shed light on the complex biology of diseases associated with the dysregulation of lysine methylation on both histones and non-histone proteins.

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Negative Regulation of Interferon-induced Transmembrane Protein 3 by SET7-mediated Lysine Monomethylation

Cited by 45 publications

References 32 publications

Set7 Facilitates Hepatitis C Virus Replication via Enzymatic Activity–Dependent Attenuation of the IFN-Related Pathway

Set7 Facilitates Hepatitis C Virus Replication via Enzymatic Activity–Dependent Attenuation of the IFN-Related Pathway

Phosphorylation of the Antiviral Protein Interferon-inducible Transmembrane Protein 3 (IFITM3) Dually Regulates Its Endocytosis and Ubiquitination

Emerging roles of lysine methylation on non-histone proteins

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