Interferon, gamma-inducible protein 16, also known as IFI16, is a human gene.
This gene encodes a member of the HIN-200 (hematopoietic interferon-inducible nuclear antigens with 200 amino acid repeats) family of cytokines. The encoded protein contains domains involved in DNA binding, transcriptional regulation, and protein-protein interactions. The protein localizes to the nucleoplasm and nucleoli, and interacts with p53 and retinoblastoma-1. It modulates p53 function, and inhibits cell growth in the Ras/Raf signaling pathway.
CHEMICAL STRUCTURE AND IMAGES
When relevant for the function
- Primary structure
Molecular weight and Size: 88,256 Da, 785 aminoacids
- Secondary structure
- Tertiary structure
- Quaternary structure
Protein Aminoacids Percentage
IFI16 and PIAS3 Aminoacids %
PIAS3 PCNA Ki67
SYNTHESIS AND TURNOVER
IFNs alpha and gamma both induce IFI16 mRNA expression in myeloid cells.
IFI16 as a negative regulator in the regulation of p53 and p21, 2003
The p200 family protein p204 as a modulator of cell proliferation and differentiation: a brief survey 2010
- The expression of the murine p200 family protein p204 in numerous tissues can be activated by a variety of distinct, tissue-specific transcription factors. p204 modulates cell proliferation, cell cycling, and the differentiation of various tissues, including skeletal muscle myotubes, beating cardiac myocytes, osteoblasts, chondrocytes, and macrophages. This protein modulates these processes in various ways, such as by
- blocking ribosomal RNA synthesis in the nucleolus
- inhibiting Ras signaling in the cytoplasm
- promoting the activity of particular transcription factors in the nucleus by forming complexes with them
- overcoming the block of the activity of other transcription factors by inhibitor of differentiation (Id) proteins.
Much remains to be learned about p204, particularly with respect to its expected involvement in the differentiation of several as yet unexplored tissues.
Immunohistochemical expression analysis of the human interferon-inducible gene IFI16, a member of the HIN200 family, not restricted to hematopoietic cells. J Interferon Cytokine Res. 22 (7): 815-21, 2002
A novel autoantigen to differentiate limited cutaneous systemic sclerosis from diffuse cutaneous systemic sclerosis: the interferon-inducible gene IFI16. Arthritis Rheum. 2006
IFI16 Is an Essential Mediator of Growth Inhibition, but Not Differentiation, Induced by the Leukemia Inhibitory Factor/JAK/STAT Pathway in Medullary Thyroid Carcinoma Cells, THE JOURNAL OF BIOLOGICAL CHEMISTRY Vol. 280, No. 6, Issue of February 11, pp. 4913–4920, 2005
Modifications of protein and amino acid metabolism during inflammation and immune system activation, Livestock Production Science 87 (2004) 37–45
Role of IFI16 in DNA damage and checkpoint. 2008
IFI16 is a member of the HIN-200 family (hematopoietic interferon-inducible nuclear antigens with 200 amino acid repeat) that contains a DNA binding domain, a transcriptional regulatory domain, DAPIN/PAAD domain associated with interferon (IFN) response and a binding domain for BRCA1, breast cancer tumor suppressor protein. IFI16 has been identified as a target of IFNa and g and is a member of the HIN-200 family. Although series of initial studies have demonstrated a potential activity of IFI16, a physiological role of the protein was largely unknown. A novel insight of the function of IFI16 stemmed from the observation that IFI16 constitutively binds to BRCA1 breast cancer tumor suppressor. Furthermore, it has been demonstrated that IFI16 is involved in p53-mediated regulation of cell growth and apoptosis. Immunocytochemical and immunohistological analyses of breast cancer cell lines and specimens revealed that levels of IFI16 are frequently decreased, supporting the notion that loss of IFI16 is closely associated with tumor development. Finally, siRNA-mediated depletion of IFI16 induces levels of NBS1, nijmegen breakage syndrome protein 1, leading to activation of DNA-PK (DNA-dependent kinase), phosphorylation of p53 Ser37 and accumulation of p21WAF1. Localization of IFI16 is determined by the status of BRCA1 protein under conditions of DNA damage, such as ionizing radiation (IR). More recently, it has been shown that levels of IFI16 are increased by oxidative stress. Together, these results illustrate that IFI16 is involved in DNA damage signaling and cell cycle checkpoint.