Gamma-interferon-inducible protein Ifi-16 (Ifi-16) also known as interferon-inducible myeloid differentiation transcriptional activator is a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
that in humans is encoded by the ''IFI16''
gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...
.
Function
This gene encodes a member of the HIN-200 (hematopoietic interferon-inducible nuclear antigens with 200 amino acid repeats) family of
cytokine
Cytokines are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in autocrin ...
s. The encoded protein contains domains involved in DNA binding, transcriptional regulation, and protein-protein interactions. The protein localizes to the
nucleoplasm
The nucleoplasm, also known as karyoplasm, is the type of protoplasm that makes up the cell nucleus, the most prominent organelle of the eukaryotic cell. It is enclosed by the nuclear envelope, also known as the nuclear membrane. The nucleoplasm ...
and
nucleoli
The nucleolus (, plural: nucleoli ) is the largest structure in the nucleus of eukaryotic cells. It is best known as the site of ribosome biogenesis, which is the synthesis of ribosomes. The nucleolus also participates in the formation of s ...
, and interacts with
p53
p53, also known as Tumor protein P53, cellular tumor antigen p53 (UniProt name), or transformation-related protein 53 (TRP53) is a regulatory protein that is often mutated in human cancers. The p53 proteins (originally thought to be, and often s ...
,
retinoblastoma-1 and
BRCA1
Breast cancer type 1 susceptibility protein is a protein that in humans is encoded by the ''BRCA1'' () gene. Orthologs are common in other vertebrate species, whereas invertebrate genomes may encode a more distantly related gene. ''BRCA1'' is a h ...
. It modulates p53 function, and inhibits cell growth in the
Ras/Raf signaling pathway.
IFI16 has been shown to play a role in the sensing of intracellular
DNA - a hallmark of virally infected cells - and has also been linked to the death of
HIV
The human immunodeficiency viruses (HIV) are two species of ''Lentivirus'' (a subgroup of retrovirus) that infect humans. Over time, they cause acquired immunodeficiency syndrome (AIDS), a condition in which progressive failure of the immune ...
-infected
helper CD4 T cells by
pyroptosis Pyroptosis is a highly inflammatory form of lytic programmed cell death that occurs most frequently upon infection with intracellular pathogens and is likely to form part of the antimicrobial response. This process promotes the rapid clearance of va ...
, a highly inflammatory form of programmed cell death.
Recently, it has been shown how IFI16, once extracellularly released, can induce inflammation upon
TLR4
Toll-like receptor 4 is a protein that in humans is encoded by the ''TLR4'' gene. TLR4 is a transmembrane protein, member of the toll-like receptor family, which belongs to the pattern recognition receptor (PRR) family. Its activation leads to an ...
binding, acting as a
DAMP.
[Iannucci A, Caneparo V, Raviola S, Debernardi I, Colangelo D, et al. (2020) Toll-like receptor 4-mediated inflammation triggered by extracellular IFI16 is enhanced by lipopolysaccharide binding. PLOS Pathogens 16(9): e1008811. https://doi.org/10.1371/journal.ppat.1008811]
References
Further reading
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External links
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Transcription factors
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