GBP2
Interferon-induced guanylate-binding protein 2 is a protein that in humans is encoded by the GBP2 gene.[5][6] GBP2 is a gene related to the superfamily of large GTPases which can be induced mainly by interferon gamma.[7]
Localization
GBP2 gene is located in a various compartment in the cell: nucleus, cytosol and cytoskeleton and also the dimer GBP2-GBP5 localise to the Golgi apparatus.[8]
In addition, the Isoprenylation is required to regulate the intracellular localization and the membrane association of GBP2.[9]
Activation
The murine GBP2 gene is not just highly activated by the interferon-gamma during macrophages activation but also by the stimulation of Toll-like receptors, Tumor necrosis factor (TNF) and Interleukin 1 beta.[10]
Expression
After the stimulation of interferon gamma, GPB2 murine is expressed in the innate and adaptive immune cells.[11]
Structure
Sequence analysis of GBP2 showed the presence of an RNA binding domain which comprises a three RNA recognition motifs (RRM) and SR domain. The amino terminus of GBp2 shares a four Arg-Gly-Gly (RGG) repeat motifs and nine serine residues in the context of arginine/serine motifs.[12]
The SR domain of GBP2 is a phosphorylation site for SR specific protein kinase SRPK (sky1) which lead a nuclear localization of GBP2.[12]
The porcine GBP2 present a high similarity regarding the N-terminal which present a globular domain and contain the GTPase function. However, the C-terminal present a helical domain which is less conserved.[13]
Interaction
GBP2 gene can interact with the RNA via the domain RRM1 and RRM2. The RRM2 domain can recognize the core motif GGUC present in the RNA. Besides, a new type of RRM domain are identified and can interact with THO/TREX complex.[14]
GBp2 gene can cooperate with TREX (transcription- export) complex; a multimeric complex has different transcription factor and exports factors such as Yra1 and Sub2.[14]
Function
Interferons are cytokines that have antiviral effects and inhibit tumor cell proliferation. They induce a large number of genes in their target cells, including those coding for the guanylate-binding proteins (GBPs). GBPs are characterized by their ability to specifically bind guanine nucleotides (GMP, GDP, and GTP). The protein encoded by this gene is a GTPase that converts GTP to GDP and GMP.[6] In addition, GBP2 gene can be a relationship between cell surface receptor and intracellular effectors which can transmit extracellular information into the cells as well as an intracellular signal transduction protein.[15]
A study on the bovine GBP2 gene showed the importance of GBP2 in the regulation of cell proliferation and the resistance to the pathogen infection such as an Exhibition of antiviral activity against influenza virus.[11]
GPB2 Promote an oxidative killing and deliver antimicrobial peptides to autophagolysosomal, providing broad host protection against different pathogen classes. During a viral infection, GBPs Family(GBP1, GBP2 and GBP5) play a vital role to activate canonical and non-canonical inflammasome to response to a pathogen infection via chlamydia muridarum.[16]
Clinical significance
Gene Mutation
A missense mutation of the GBP2 (A907G) has been identified in patients of a migraine. In the first step can lead to vasomotor dysfunction and then headaches.[15]
Breast cancer
GBP2 is considered as a control factor for the proliferation and spreading in the tumor cell. The high expression of GBP2 is associated with a better diagnosis of breast cancer. P53 can upregulate GBP2 and play an essential role in the tumor development by inhibition of metalloproteinase MM9 as well as NF-Kappa B and Rac protein.[17]
The transcriptional level of GBP2 is also regulated by two transcription factor STAT1 and IRF1. GBP2 expression have a strong correlation with T cell metagene which seems an association with the infiltration of T cell in the breast cancer.[17]
However, a recent study showed that GBP2 can regulate dynamin-related protein 1 (Drp1) to block the translocation of Drp1 to the mitochondria which lead to an attenuation of the Drp1 dependent mitochondrial fission and also an invasion of breast cancer cells.[18]
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000162645 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000028270 – 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.
- ^ Cheng YS, Patterson CE, Staeheli P (September 1991). "Interferon-induced guanylate-binding proteins lack an N(T)KXD consensus motif and bind GMP in addition to GDP and GTP". Molecular and Cellular Biology. 11 (9): 4717–25. doi:10.1128/mcb.11.9.4717. PMC 361367. PMID 1715024.
- ^ a b "Entrez Gene: GBP2 guanylate binding protein 2, interferon-inducible".
- ^ Kim BH, Shenoy AR, Kumar P, Bradfield CJ, MacMicking JD (October 2012). "IFN-inducible GTPases in host cell defense". Cell Host & Microbe. 12 (4): 432–44. doi:10.1016/j.chom.2012.09.007. PMC 349020. PMID 23084913.
- ^ "GBP2 Gene". GeneCards Human Gene Database. Retrieved 2018-11-07.
- ^ Britzen-Laurent N, Bauer M, Berton V, Fischer N, Syguda A, Reipschläger S, Naschberger E, Herrmann C, Stürzl M (December 2010). "Intracellular trafficking of guanylate-binding proteins is regulated by heterodimerization in a hierarchical manner". PLOS ONE. 5 (12): e14246. Bibcode:2010PLoSO...514246B. doi:10.1371/journal.pone.0014246. PMC 2998424. PMID 21151871.
- ^ Degrandi D, Kravets E, Konermann C, Beuter-Gunia C, Klümpers V, Lahme S, Wischmann E, Mausberg AK, Beer-Hammer S, Pfeffer K (January 2013). "Murine guanylate binding protein 2 (mGBP2) controls Toxoplasma gondii replication". Proceedings of the National Academy of Sciences of the United States of America. 110 (1): 294–9. Bibcode:2013PNAS..110..294D. doi:10.1073/pnas.1205635110. PMC 3538222. PMID 23248289.
- ^ a b Praefcke GJ (November 2017). "Regulation of innate immune functions by guanylate-binding proteins". International Journal of Medical Microbiology. 308 (1): 237–245. doi:10.1016/j.ijmm.2017.10.013. PMID 29174633.
- ^ a b Windgassen M, Krebber H (March 2003). "Identification of Gbp2 as a novel poly(A)+ RNA-binding protein involved in the cytoplasmic delivery of messenger RNAs in yeast". EMBO Reports. 4 (3): 278–83. doi:10.1038/sj.embor.embor763. PMC 1315891. PMID 12634846.
- ^ Ma G, Huang J, Sun N, Liu X, Zhu M, Wu Z, Zhao S (May 2008). "Molecular characterization of the porcine GBP1 and GBP2 genes". Molecular Immunology. 45 (10): 2797–807. doi:10.1016/j.molimm.2008.02.007. PMID 18346789.
- ^ a b Martínez-Lumbreras S, Taverniti V, Zorrilla S, Séraphin B, Pérez-Cañadillas JM (January 2016). "Gbp2 interacts with THO/TREX through a novel type of RRM domain". Nucleic Acids Research. 44 (1): 437–48. doi:10.1093/nar/gkv1303. PMC 4705658. PMID 26602689.
- ^ a b Jiang, Yue (January 2016). "Six novel rare non-synonymous mutations for migraine without aura identified by exome sequencing". Journal of Neurogenetics. 29 (4): 188–194. doi:10.3109/01677063.2015.1122787. PMID 26814133. S2CID 207441191.
- ^ Man SM, Place DE, Kuriakose T, Kanneganti TD (January 2017). "Interferon-inducible guanylate-binding proteins at the interface of cell-autonomous immunity and inflammasome activation". Journal of Leukocyte Biology. 101 (1): 143–150. doi:10.1189/jlb.4MR0516-223R. PMC 6608036. PMID 27418355.
- ^ a b Godoy P, Cadenas C, Hellwig B, Marchan R, Stewart J, Reif R, Lohr M, Gehrmann M, Rahnenführer J, Schmidt M, Hengstler JG (July 2014). "Interferon-inducible guanylate binding protein (GBP2) is associated with better prognosis in breast cancer and indicates an efficient T cell response". Breast Cancer. 21 (4): 491–9. doi:10.1007/s12282-012-0404-8. PMID 23001506. S2CID 8338232.
- ^ Zhang J, Zhang Y, Wu W, Wang F, Liu X, Shui G, Nie C (October 2017). "Guanylate-binding protein 2 regulates Drp1-mediated mitochondrial fission to suppress breast cancer cell invasion". Cell Death & Disease. 8 (10): e3151. doi:10.1038/cddis.2017.559. PMC 5680924. PMID 29072687.
Further reading
- Maruyama K, Sugano S (January 1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
- Neun R, Richter MF, Staeheli P, Schwemmle M (July 1996). "GTPase properties of the interferon-induced human guanylate-binding protein 2". FEBS Letters. 390 (1): 69–72. doi:10.1016/0014-5793(96)00628-X. PMID 8706832. S2CID 30513363.
- Nitsche EM, Moquin A, Adams PS, Guenette RS, Lakins JN, Sinnecker GH, Kruse K, Tenniswood MP (May 1996). "Differential display RT PCR of total RNA from human foreskin fibroblasts for investigation of androgen-dependent gene expression". American Journal of Medical Genetics. 63 (1): 231–8. doi:10.1002/(SICI)1096-8628(19960503)63:1<231::AID-AJMG40>3.0.CO;2-M. PMID 8723115.
- Vestal DJ, Gorbacheva VY, Sen GC (November 2000). "Different subcellular localizations for the related interferon-induced GTPases, MuGBP-1 and MuGBP-2: implications for different functions?". Journal of Interferon & Cytokine Research. 20 (11): 991–1000. doi:10.1089/10799900050198435. PMID 11096456.
- Lukasiewicz R, Velazquez-Dones A, Huynh N, Hagopian J, Fu XD, Adams J, Ghosh G (August 2007). "Structurally unique yeast and mammalian serine-arginine protein kinases catalyze evolutionarily conserved phosphorylation reactions". The Journal of Biological Chemistry. 282 (32): 23036–43. doi:10.1074/jbc.M611305200. PMID 17517895.