Редактирование: IFI16

Gamma-interferon-inducible protein 16 (Ifi-16) (Interferon-inducible myeloid differentiation transcriptional activator) [IFNGIP1]

==Publications==

{{medline-entry
|title=Transcriptomic analysis of purified human cortical microglia reveals age-associated changes.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/28671693
|abstract=Microglia are essential for CNS homeostasis and innate neuroimmune function, and play important roles in neurodegeneration and brain aging. Here we present gene expression profiles of purified microglia isolated at autopsy from the parietal cortex of 39 human subjects with intact cognition. Overall, genes expressed by human microglia were similar to those in mouse, including established microglial genes [[CX3CR1]], [[P2RY12]] and [[ITGAM]] (CD11B). However, a number of immune genes, not identified as part of the mouse microglial signature, were abundantly expressed in human microglia, including TLR, Fcγ and SIGLEC receptors, as well as [[TAL1]] and [[IFI16]], regulators of proliferation and cell cycle. Age-associated changes in human microglia were enriched for genes involved in cell adhesion, axonal guidance, cell surface receptor expression and actin (dis)assembly. Limited overlap was observed in microglial genes regulated during aging between mice and humans, indicating that human and mouse microglia age differently.
|mesh-terms=* Aging
* Axons
* Brain
* CD11b Antigen
* Cell Cycle
* Gene Expression
* Gene Expression Profiling
* Humans
* Microglia

|full-text-url=https://sci-hub.do/10.1038/nn.4597
}}
{{medline-entry
|title=[[IFI16]], an amplifier of DNA-damage response: Role in cellular senescence and aging-associated inflammatory diseases.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/27063514
|abstract=DNA-damage induces a DNA-damage response (DDR) in mammalian cells. The response, depending upon the cell-type and the extent of DNA-damage, ultimately results in cell death or cellular senescence. DDR-induced signaling in cells activates the [[ATM]]-p53 and [[ATM]]-IKKα/β-interferon (IFN)-β signaling pathways, thus leading to an induction of the p53 and IFN-inducible [[IFI16]] gene. Further, upon DNA-damage, DNA accumulates in the cytoplasm, thereby inducing the [[IFI16]] protein and STING-dependent IFN-β production and activation of the [[IFI16]] inflammasome, resulting in the production of proinflammatory cytokines (e.g., IL-1β and IL-18). Increased expression of [[IFI16]] protein in a variety of cell-types promotes cellular senescence. However, reduced expression of [[IFI16]] in cells promotes cell proliferation. Because expression of the [[IFI16]] gene is induced by activation of DNA-damage response in cells and increased levels of [[IFI16]] protein in cells potentiate the p53-mediated transcriptional activation of genes and p53 and pRb-mediated cell cycle arrest, we discuss how an improved understanding of the role of [[IFI16]] protein in cellular senescence and associated inflammatory secretory phenotype is likely to identify the molecular mechanisms that contribute to the development of aging-associated human inflammatory diseases and a failure to cancer therapy.
|mesh-terms=* Aging
* Cellular Senescence
* DNA Damage
* Humans
* Inflammasomes
* Nuclear Proteins
* Phosphoproteins
* Signal Transduction
* Transcriptional Activation
* Tumor Suppressor Protein p53
|keywords=* Cancer
* Cellular senescence
* DNA-damage
* IFI16
* Inflammation
* Interferon
* p53
|full-text-url=https://sci-hub.do/10.1016/j.arr.2016.04.002
}}
{{medline-entry
|title=Genomic regulation of senescence and innate immunity signaling in the retinal pigment epithelium.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/25963977
|abstract=The tumor suppressor p53 is a major regulator of genes important for cell cycle arrest, senescence, apoptosis, and innate immunity, and has recently been implicated in retinal aging. In this study we sought to identify the genetic networks that regulate p53 function in the retina using quantitative trait locus (QTL) analysis. First we examined age-associated changes in the activation and expression levels of p53; known p53 target proteins and markers of innate immune system activation in primary retinal pigment epithelial ([[RPE]]) cells that were harvested from young and aged human donors. We observed increased expression of p53, activated caspase-1, [[CDKN1A]], [[[[CDKN2A]]]] (p16INK4a), [[TLR4]], and IFNα in aged primary [[RPE]] cell lines. We used the Hamilton Eye Institute (HEI) retinal dataset ( www.genenetwork.org ) to identify genomic loci that modulate expression of genes in the p53 pathway in recombinant inbred BXD mouse strains using a QTL systems biology-based approach. We identified a significant trans-QTL on chromosome 1 (region 172-177 Mb) that regulates the expression of Cdkn1a. Many of the genes in this QTL locus are involved in innate immune responses, including Fc receptors, interferon-inducible family genes, and formin 2. Importantly, we found an age-related increase in [[FCGR3A]] and [[FMN2]] and a decrease in [[IFI16]] levels in [[RPE]] cultures. There is a complex multigenic innate immunity locus that controls expression of genes in the p53 pathway in the [[RPE]], which may play an important role in modulating age-related changes in the retina.
|mesh-terms=* Adult
* Aged, 80 and over
* Aging
* Animals
* Apoptosis
* Caspases
* Caspases, Initiator
* Cell Line
* Cyclin-Dependent Kinase Inhibitor p16
* Cyclin-Dependent Kinase Inhibitor p21
* Gene Expression Regulation
* Humans
* Immunity, Innate
* Interferon-alpha
* Interferon-gamma
* Mice
* Mice, Inbred BALB C
* Mice, Inbred C57BL
* Mice, Inbred DBA
* Primary Cell Culture
* Quantitative Trait Loci
* Retinal Pigment Epithelium
* Signal Transduction
* Toll-Like Receptor 4
* Tumor Suppressor Protein p53

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4450138
}}