Interferon Signaling Modulation Pathway

Preferred Label : Interferon Signaling Modulation Pathway;

NCIt related terms : Chaperones modulate interferon Signaling Pathway;

Alternative definition : BIOCARTA: Signaling by interferon-gamma stimulates anti-viral responses and tumor suppression through the heterodimeric interferon-gamma receptor. Signaling is initiated by binding of interferon-gamma to its receptor, activating the receptor-associated JAK2 tyrosine kinase to phosphorylate STAT transcription factors that activate interferon responsive genes. Molecular chaperones that modulate or alter protein folding interact with different components of the interferon signaling pathway. One chaperone that modulates interferon signaling is hTid-1, a member of the DnaJ family of chaperones and a co-chaperone for the heat shock protein Hsp70, another molecular chaperone. hTid-1 was found in a two-hybrid screen to bind to JAK2 and also to interact with the interferon-gamma receptor. In addition, hTid-1 and JAK2 also interact with Hsp70. Overexpression of hTid-1 represses transcriptional activation by interferon-gamma and Hsp70 dissociates from these proteins when interferon is added to cells, suggesting that Hsp70 holds Jak2 in an inactive conformation prior to ligand activation, and is released in the presence of agonist to allow the activation of Jak-2 and downstream pathways. hTid-1 and Hsp-70 interact with other signaling proteins as well. One of these is Tax, a protein encoded by the HTLV-1 virus that binds to hTid-1. hTid-1 also represses NF-kB activation by blocking the phosphorylation and inactivation of I-kappaB by the IkappaB kinase beta. Hsp70 plays a significant role in protein unfolding for entry into mitochondria and also interacts with tumor suppressor gene products to produce their anti-proliferative activity. One of the actions of interferon is to induce apoptosis of infected target cells, in part through a mitochondrial dependent mechanism. An interaction between interferon signaling and Hsp70 may alter this mitochondrial apoptosis pathway, perhaps playing a role in interferon-mediated apoptosis of infected or transformed cells. The HTLV-1 Tax protein that interacts with Hsp70 blocks mitochondrial induced apoptosis, providing a protection against interferon-mediated cellular defenses. (This definition may be outdated - see the DesignNote.);

NCIt note : The BIOCARTA Definition (ALT_DEFINITION) for this pathway concept was provided by BioCarta. This property was not created by, nor is it maintained by the NCI Thesaurus staff. Additionally, BioCarta is no longer updating its pathway data; thus, the BIOCARTA Definition might be outdated or inaccurate. Please see the Terms and Conditions for Use at http://www.biocarta.com/.;

Biocarta ID : h_tidPathway;

Details

Origin ID

C39253;

UMLS CUI

C1512834;

Semantic type(s)
- Molecular Function [UMLS semantic type]
has_gene_product_element
- Cellular Tumor Antigen p53 [NCIt concept]
- Heat Shock 70 kDa Protein 1A/1B [NCIt concept]
- Interferon Gamma [NCIt concept]
- Interferon Gamma Receptor 1 [NCIt concept]
- Interferon Gamma Receptor 2 [NCIt concept]
- NF-Kappa-B Inhibitor Alpha [NCIt concept]
- Retinoblastoma-Associated Protein [NCIt concept]
- Thioredoxin [NCIt concept]
- Transcription Factor p65 [NCIt concept]
- Tumor Necrosis Factor [NCIt concept]
- Tumor Necrosis Factor Receptor Superfamily Member 1A [NCIt concept]
- Tyrosine-Protein Kinase JAK2 [NCIt concept]
- Wilms Tumor Protein [NCIt concept]
pathway_has_gene_element
- HSPA1A wt Allele [NCIt concept]
- HSPA1B wt Allele [NCIt concept]
- IFNG wt Allele [NCIt concept]
- IFNGR1 wt Allele [NCIt concept]
- IFNGR2 wt Allele [NCIt concept]
- JAK2 wt Allele [NCIt concept]
- NFKBIA wt Allele [NCIt concept]
- RB1 wt Allele [NCIt concept]
- RELA wt Allele [NCIt concept]
- TNF wt Allele [NCIt concept]
- TNFRSF1A wt Allele [NCIt concept]
- TP53 wt Allele [NCIt concept]
- TXN wt Allele [NCIt concept]
- WT1 wt Allele [NCIt concept]

Keyword's position in hierarchy(ies) :

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