| Structural highlights
Function
IN35_HUMAN Acts as a signaling pathway regulator involved in innate immune system response (PubMed:26342464, PubMed:29038465, PubMed:29350881). In response to interferon IFN-alpha, associates in a complex with signaling pathway regulator NMI to regulate immune response; the complex formation prevents proteasome-mediated degradation of IFI35 and correlates with IFI35 dephosphorylation (PubMed:10779520, PubMed:10950963). In complex with NMI, inhibits virus-triggered type I interferon/IFN-beta production (PubMed:26342464). In complex with NMI, negatively regulates nuclear factor NF-kappa-B signaling by inhibiting the nuclear translocation, activation and transcription of the NF-kappa-B subunit p65/RELA, resulting in the inhibition of endothelial cell proliferation, migration and re-endothelialization of injured arteries (PubMed:29350881). Beside its role as an intracellular signaling pathway regulator, also functions extracellularly as damage-associated molecular patterns (DAMPs) to promote inflammation when actively released by macrophage to the extracellular space during cell injury and pathogen invasion (PubMed:29038465). Macrophage-secreted IFI35 activates NF-kappa-B signaling in adjacent macrophages through Toll-like receptor 4/TLR4 activation, thereby inducing NF-kappa-B translocation from the cytoplasm into the nucleus which promotes the release of pro-inflammatory cytokines (PubMed:29038465).[1] [2] [3] [4] [5]
References
- ↑ Zhou X, Liao J, Meyerdierks A, Feng L, Naumovski L, Bottger EC, Omary MB. Interferon-alpha induces nmi-IFP35 heterodimeric complex formation that is affected by the phosphorylation of IFP35. J Biol Chem. 2000 Jul 14;275(28):21364-71. doi: 10.1074/jbc.M003177200. PMID:10779520 doi:https://dx.doi.org/10.1074/jbc.M003177200
- ↑ Chen J, Shpall RL, Meyerdierks A, Hagemeier M, Bottger EC, Naumovski L. Interferon-inducible Myc/STAT-interacting protein Nmi associates with IFP 35 into a high molecular mass complex and inhibits proteasome-mediated degradation of IFP 35. J Biol Chem. 2000 Nov 17;275(46):36278-84. doi: 10.1074/jbc.M006975200. PMID:10950963 doi:https://dx.doi.org/10.1074/jbc.M006975200
- ↑ Das A, Dinh PX, Pattnaik AK. Trim21 regulates Nmi-IFI35 complex-mediated inhibition of innate antiviral response. Virology. 2015 Nov;485:383-92. PMID:26342464 doi:10.1016/j.virol.2015.08.013
- ↑ Xiahou Z, Wang X, Shen J, Zhu X, Xu F, Hu R, Guo D, Li H, Tian Y, Liu Y, Liang H. NMI and IFP35 serve as proinflammatory DAMPs during cellular infection and injury. Nat Commun. 2017 Oct 16;8(1):950. PMID:29038465 doi:10.1038/s41467-017-00930-9
- ↑ Jian D, Wang W, Zhou X, Jia Z, Wang J, Yang M, Zhao W, Jiang Z, Hu X, Zhu J. Interferon-induced protein 35 inhibits endothelial cell proliferation, migration and re-endothelialization of injured arteries by inhibiting the nuclear factor-kappa B pathway. Acta Physiol (Oxf). 2018 Jul;223(3):e13037. PMID:29350881 doi:10.1111/apha.13037
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