TRIM25
| TRIM25 | |||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| |||||||||||||||||||||||||||||||||||||||||||||||||||
| Identifiers | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Aliases | TRIM25, EFP, RNF147, Z147, ZNF147, tripartite motif containing 25 | ||||||||||||||||||||||||||||||||||||||||||||||||||
| External IDs | OMIM: 600453; MGI: 102749; HomoloGene: 48325; GeneCards: TRIM25; OMA:TRIM25 - orthologs | ||||||||||||||||||||||||||||||||||||||||||||||||||
| EC number | 2.3.2.27 | ||||||||||||||||||||||||||||||||||||||||||||||||||
| |||||||||||||||||||||||||||||||||||||||||||||||||||
| |||||||||||||||||||||||||||||||||||||||||||||||||||
| |||||||||||||||||||||||||||||||||||||||||||||||||||
| |||||||||||||||||||||||||||||||||||||||||||||||||||
| |||||||||||||||||||||||||||||||||||||||||||||||||||
| Wikidata | |||||||||||||||||||||||||||||||||||||||||||||||||||
| |||||||||||||||||||||||||||||||||||||||||||||||||||
Tripartite motif-containing protein 25 is a protein that in humans is encoded by the TRIM25 gene.[5][6]
Function
The protein encoded by this gene is a member of the tripartite motif (TRIM) family grouping more than 70 TRIMs. TRIM proteins primarily function as ubiquitin ligases that regulate the innate response to infection.[7] TRIM25 localizes to the cytoplasm. The presence of potential DNA-binding and dimerization-transactivation domains suggests that this protein may act as a transcription factor, similar to several other members of the TRIM family. Expression of the gene is upregulated in response to estrogen, and it is thought to mediate estrogen actions in breast cancer as a primary response gene.[6]
Domain Architecture
TRIM25 has an N-terminal RING domain, followed by a B-box type 1 domain, a B-box type 2 domain, a coiled-coil domain (CCD) and a C-terminal SPRY domain. The RING domain coordinates two zinc atoms and is essential for recruiting ubiquitin-conjugating enzymes. The function of the B-box domains is unknown. The CCD domain has been implicated in multimerization and other protein-protein interactions.[8] The SPRY domain is required for substrate recruitment.[9] The NMR chemical shifts for backbone of the PRYSPRY domain of TRIM25 is assigned based on triple-resonance experiments using uniformly isotopic labeled protein and the secondary structure of the domain PRYSPRY domain of TRIM25 predicted based on the NMR assignments.[10]
TRIM25 functions
TRIM25 plays a key role in the RIG-I signaling pathway. RIG-I is a cytosolic pattern recognition receptor that senses viral RNA. Following RNA recognition, the caspase recruitment domain (CARD) of RIG-I undergoes K(63)-linked ubiquitination by TRIM25. The RING and SPRY domains of TRIM25 mediate its interaction with RIG-I. IFN production then follows by an intracellular signaling pathway involving IRF3.[11] Results obtained in human TRIM25 knock-out cells suggest that it may not play a key role in RIG-I activation.[12][13][14] These studies revealed that another E3 ubiquitin ligase RIPLET (RNF135), not TRIM25, is sufficient to ubiquitinate and activate the RIG-I.
TRIM25 has been shown to be an RNA-binding protein. [15][16][17] TRIM25 binds RNAs (either single- or double-stranded) through an RNA-binding domain (RBD) residing in its C-terminal PRY/SPRY region in conjunction with CCD. [18][19] RNA-binding appears to be important for TRIM25 ubiquitin ligase activity.[18] Some data suggest that it can destabilise viral mRNA. [14]
- ^ a b c GRCh38: Ensembl release 89: ENSG00000121060 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000000275 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ Inoue S, Orimo A, Matsuda Y, Inazawa J, Emi M, Nakamura Y, Hori T, Muramatsu M (Jan 1995). "Chromosome mapping of human (ZNF147) and mouse genes for estrogen-responsive finger protein (efp), a member of the RING finger family". Genomics. 25 (2): 581–3. doi:10.1016/0888-7543(95)80064-S. PMID 7789997.
- ^ a b "Entrez Gene: TRIM25 tripartite motif-containing 25".
- ^ D'Cruz AA, Kershaw NJ, Chiang JJ, Wang MK, Nicola NA, Babon JJ, Gack MU, Nicholson SE (2013). "Crystal structure of the TRIM25 B30.2 (PRYSPRY) domain: a key component of antiviral signalling". The Biochemical Journal. 456 (2): 231–40. doi:10.1042/BJ20121425. PMC 4012390. PMID 24015671.
- ^ Haik KG (Jul 1985). "Visual difficulties from video display terminals". Southern Medical Journal. 78 (7): 887–8. doi:10.1097/00007611-198507000-00031. PMID 4012390.
- ^ Pilka L, Trávník P, Dvorák M, Tesarík J, Ventruba P, Krejcí K, Soska J (Aug 1985). "[Delivery after intrauterine embryo transfer obtained by fertilization and oocyte culture in vitro]". Ceskoslovenská Gynekologie. 50 (7): 452–9. PMID 4042170.
- ^ Kong C, Penumutchu SR, Hung Kw, Huang H, Lin T, Yu C (2015-02-22). "Backbone resonance assignments of the PRYSPRY domain of TRIM25". Biomolecular NMR Assignments. 9 (2): 313–315. doi:10.1007/s12104-015-9599-x. ISSN 1874-2718. PMID 25702035. S2CID 11475584.
- ^ Gack MU, Kirchhofer A, Shin YC, Inn KS, Liang C, Cui S, Myong S, Ha T, Hopfner KP, Jung JU (Oct 2008). "Roles of RIG-I N-terminal tandem CARD and splice variant in TRIM25-mediated antiviral signal transduction". Proceedings of the National Academy of Sciences of the United States of America. 105 (43): 16743–8. Bibcode:2008PNAS..10516743G. doi:10.1073/pnas.0804947105. PMC 2575490. PMID 18948594.
- ^ Cadena C, Ahmad S, Xavier A, Willemsen J, Park S, Park JW, Oh SW, Fujita T, Hou F, Binder M, Hur S (2019). "Ubiquitin-Dependent and -Independent Roles of E3 Ligase RIPLET in Innate Immunity". Cell. 177 (5): 1187–1200.e16. doi:10.1016/j.cell.2019.03.017. PMC 6525047. PMID 31006531.
- ^ Hayman TJ, Hsu AC, Kolesnik TB, Dagley LF, Willemsen J, Tate MD, Baker PJ, Kershaw NJ, Kedzierski L, Webb AI, Wark PA, Kedzierska K, Masters SL, Belz GT, Binder M (2019). "RIPLET, and not TRIM25, is required for endogenous RIG-I-dependent antiviral responses". Immunology & Cell Biology. 97 (9): 840–852. doi:10.1111/imcb.12284. ISSN 0818-9641. PMID 31335993.
- ^ a b Choudhury NR, Trus I, Heikel G, Wolczyk M, Szymanski J, Bolembach A, DosSantosPinto RM, Smith N, Trubitsyna M, Gaunt E, Digard P, Michlewski G (2022). "TRIM25 inhibits influenza A virus infection, destabilizes viral mRNA, but is redundant for activating the RIG-I pathway". Nucleic Acids Research. 50 (12): 7097–7114. doi:10.1093/nar/gkac512. ISSN 0305-1048. PMC 9262604. PMID 35736141.
- ^ Choudhury NR, Nowak J, Zuo J, Rappsilber J, Spoel SH, Michlewski G (2014). "Trim25 Is an RNA-Specific Activator of Lin28a/TuT4-Mediated Uridylation". Cell Reports. 9 (4): 1265–1272. doi:10.1016/j.celrep.2014.10.017. PMC 4542301. PMID 25457611.
- ^ Kwon SC, Yi H, Eichelbaum K, Föhr S, Fischer B, You KT, Castello A, Krijgsveld J, Hentze MW, Kim VN (2013). "The RNA-binding protein repertoire of embryonic stem cells". Nature Structural & Molecular Biology. 20 (9): 1122–1130. doi:10.1038/nsmb.2638. ISSN 1545-9993.
- ^ Castello A, Fischer B, Eichelbaum K, Horos R, Beckmann BM, Strein C, Davey NE, Humphreys DT, Preiss T, Steinmetz LM, Krijgsveld J, Hentze MW (2012). "Insights into RNA Biology from an Atlas of Mammalian mRNA-Binding Proteins". Cell. 149 (6): 1393–1406. doi:10.1016/j.cell.2012.04.031. PMID 22658674.
- ^ a b Choudhury NR, Heikel G, Trubitsyna M, Kubik P, Nowak JS, Webb S, Granneman S, Spanos C, Rappsilber J, Castello A, Michlewski G (2017). "RNA-binding activity of TRIM25 is mediated by its PRY/SPRY domain and is required for ubiquitination". BMC Biology. 15 (1). doi:10.1186/s12915-017-0444-9. ISSN 1741-7007. PMID 29117863.
- ^ Álvarez L, Haubrich K, Iselin L, Gillioz L, Ruscica V, Lapouge K, Augsten S, Huppertz I, Choudhury NR, Simon B, Masiewicz P, Lethier M, Cusack S, Rittinger K, Gabel F (2024-10-01). "The molecular dissection of TRIM25's RNA-binding mechanism provides key insights into its antiviral activity". Nature Communications. 15 (1): 8485. Bibcode:2024NatCo..15.8485A. doi:10.1038/s41467-024-52918-x. ISSN 2041-1723. PMC 11445558. PMID 39353916.
Viral escape
To avoid IFN production, the non structural protein (NS1) of influenza will interact with CCD domain of TRIM25 to block RIG-I ubiquitination. Some studies have shown that a deletion of the CCD domain of TRIM25 prevents the binding of NS1.[5] Without this ubiquitination, there won’t be IFN production.
References
- ^ Cite error: The named reference
:2was invoked but never defined (see the help page). - ^ Cite error: The named reference
:1was invoked but never defined (see the help page). - ^ Cadena C, Ahmad S, Xavier A, Willemsen J, Park S, Park JW, Oh SW, Fujita T, Hou F, Binder M, Hur S (2019). "Ubiquitin-Dependent and -Independent Roles of E3 Ligase RIPLET in Innate Immunity". Cell. 177 (5): 1187–1200.e16. doi:10.1016/j.cell.2019.03.017. PMC 6525047. PMID 31006531.
- ^ Cite error: The named reference
:3was invoked but never defined (see the help page). - ^ Gack MU, Albrecht RA, Urano T, Inn KS, Huang IC, Carnero E, Farzan M, Inoue S, Jung JU, García-Sastre A (May 2009). "Influenza A virus NS1 targets the ubiquitin ligase TRIM25 to evade recognition by the host viral RNA sensor RIG-I". Cell Host & Microbe. 5 (5): 439–49. doi:10.1016/j.chom.2009.04.006. PMC 2737813. PMID 19454348.
Further reading
- Horie K, Urano T, Ikeda K, Inoue S (Jun 2003). "Estrogen-responsive RING finger protein controls breast cancer growth". The Journal of Steroid Biochemistry and Molecular Biology. 85 (2–5): 101–4. doi:10.1016/S0960-0760(03)00209-7. PMID 12943693. S2CID 22487508.
- Inoue S, Orimo A, Hosoi T, Kondo S, Toyoshima H, Kondo T, Ikegami A, Ouchi Y, Orimo H, Muramatsu M (Dec 1993). "Genomic binding-site cloning reveals an estrogen-responsive gene that encodes a RING finger protein". Proceedings of the National Academy of Sciences of the United States of America. 90 (23): 11117–21. Bibcode:1993PNAS...9011117I. doi:10.1073/pnas.90.23.11117. PMC 47933. PMID 8248217.
- Bonaldo MF, Lennon G, Soares MB (Sep 1996). "Normalization and subtraction: two approaches to facilitate gene discovery". Genome Research. 6 (9): 791–806. doi:10.1101/gr.6.9.791. PMID 8889548.
- Ikeda K, Inoue S, Orimo A, Sano M, Watanabe T, Tsutsumi K, Muramatsu M (Jul 1997). "Multiple regulatory elements and binding proteins of the 5'-flanking region of the human estrogen-responsive finger protein (efp) gene". Biochemical and Biophysical Research Communications. 236 (3): 765–71. doi:10.1006/bbrc.1997.7046. PMID 9245730.
- Ikeda K, Orimo A, Higashi Y, Muramatsu M, Inoue S (Apr 2000). "Efp as a primary estrogen-responsive gene in human breast cancer". FEBS Letters. 472 (1): 9–13. Bibcode:2000FEBSL.472....9I. doi:10.1016/S0014-5793(00)01421-6. PMID 10781795. S2CID 10570937.
- Reymond A, Meroni G, Fantozzi A, Merla G, Cairo S, Luzi L, Riganelli D, Zanaria E, Messali S, Cainarca S, Guffanti A, Minucci S, Pelicci PG, Ballabio A (May 2001). "The tripartite motif family identifies cell compartments". The EMBO Journal. 20 (9): 2140–51. doi:10.1093/emboj/20.9.2140. PMC 125245. PMID 11331580.
- Urano T, Saito T, Tsukui T, Fujita M, Hosoi T, Muramatsu M, Ouchi Y, Inoue S (Jun 2002). "Efp targets 14-3-3 sigma for proteolysis and promotes breast tumour growth". Nature. 417 (6891): 871–5. Bibcode:2002Natur.417..871U. doi:10.1038/nature00826. PMID 12075357. S2CID 4348545.
- Shimada N, Suzuki T, Inoue S, Kato K, Imatani A, Sekine H, Ohara S, Shimosegawa T, Sasano H (Apr 2004). "Systemic distribution of estrogen-responsive finger protein (Efp) in human tissues". Molecular and Cellular Endocrinology. 218 (1–2): 147–53. doi:10.1016/j.mce.2003.12.008. PMID 15130519. S2CID 44761828.
- Rush J, Moritz A, Lee KA, Guo A, Goss VL, Spek EJ, Zhang H, Zha XM, Polakiewicz RD, Comb MJ (Jan 2005). "Immunoaffinity profiling of tyrosine phosphorylation in cancer cells". Nature Biotechnology. 23 (1): 94–101. doi:10.1038/nbt1046. PMID 15592455. S2CID 7200157.
- Suzuki T, Urano T, Tsukui T, Horie-Inoue K, Moriya T, Ishida T, Muramatsu M, Ouchi Y, Sasano H, Inoue S (Sep 2005). "Estrogen-responsive finger protein as a new potential biomarker for breast cancer". Clinical Cancer Research. 11 (17): 6148–54. doi:10.1158/1078-0432.CCR-05-0040. PMID 16144914. S2CID 11698115.
- Nakayama H, Sano T, Motegi A, Oyama T, Nakajima T (Nov 2005). "Increasing 14-3-3 sigma expression with declining estrogen receptor alpha and estrogen-responsive finger protein expression defines malignant progression of endometrial carcinoma". Pathology International. 55 (11): 707–15. doi:10.1111/j.1440-1827.2005.01900.x. PMID 16271083. S2CID 7106422.
- Nakasato N, Ikeda K, Urano T, Horie-Inoue K, Takeda S, Inoue S (Dec 2006). "A ubiquitin E3 ligase Efp is up-regulated by interferons and conjugated with ISG15". Biochemical and Biophysical Research Communications. 351 (2): 540–6. doi:10.1016/j.bbrc.2006.10.061. PMID 17069755.
- Nakajima A, Maruyama S, Bohgaki M, Miyajima N, Tsukiyama T, Sakuragi N, Hatakeyama S (May 2007). "Ligand-dependent transcription of estrogen receptor alpha is mediated by the ubiquitin ligase EFP". Biochemical and Biophysical Research Communications. 357 (1): 245–51. doi:10.1016/j.bbrc.2007.03.134. hdl:2115/24261. PMID 17418098.