Disease relevance of IFI44

• The production of p44 mRNA is markedly induced in the liver of chimpanzees infected with hepatitis C or hepatitis D virus [1].
• The gene encoding p44, a subunit of the transcription factor TFIIH, is involved in large-scale deletions associated with Werdnig-Hoffmann disease [2].
• Our results demonstrate that IGF-I induces N-Myc in the KP-N-RT neuroblastoma cell line at the RNA level and establishes a clear correlation between N-Myc induction and activation of p44/42 MAPK signaling [3].
• These findings showed that p44 multigenes have several active expression sites and the expression is regulated at transcriptional level, suggesting a potentially unique mechanism for generating the diversity in major antigenic outer membrane proteins of the HGE agent [4].
• First, we have shown that pertussis toxin (which uncouples G-protein-coupled receptors from inhibitory G-proteins) reduced the platelet-derived growth factor stimulation of p42/p44 mitogen-activated protein kinase [5].

Psychiatry related information on IFI44

• Given the role of MAP kinases in various physiological functions and gene expression, alterations in p44/42 MAP kinase activation and expression of ERK1/2 may contribute significantly to the pathophysiology of depressive disorders [6].
• In this review we describe in vivo evidence implicating that p38 and p44/42 MAPKs may play a critical role in harmful microglial activation in acute brain injury, such as stroke, and in more chronic neurodegenerative diseases, such as Alzheimer's disease [7].
• Careful analysis of each TFIIH subunit also shows how the p44 Ring finger participates in certain promoter escape reactions [8].
• In response to the immobilization stress of rats, a useful model of emotional stress, rapid activation of p44/p42 mitogen-activated protein kinase was observed in the heart, followed by a transient upregulation of immediate early genes in the smooth muscle cells of coronary arteries, the endothelial cells and the myocardium [9].

High impact information on IFI44

• Mutations in the XPD C-terminal domain, as found in most patients, prevent the interaction with p44, thus explaining the decrease in XPD helicase activity and the nucleotide excision repair (NER) defect [10].
• Activation of chemerin receptor results in intracellular calcium release, inhibition of cAMP accumulation, and phosphorylation of p42-p44 MAP kinases, through the Gi class of heterotrimeric G proteins [11].
• Internalization does not terminate its signaling; instead, the internalized receptor is phosphorylated, codistributes with active phospholipase C-gamma, and activates p44/42 mitogen-activated protein kinase phosphorylation and cell proliferation [12].
• Nuclear translocation of p42/p44 mitogen-activated protein kinase is required for growth factor-induced gene expression and cell cycle entry [13].
• The critical region in 5q13 contains an inverted repeat harboring several genes, including the survival motor neuron (SMN) gene, the neuronal apoptosis inhibitory protein (NAIP) gene, and the p44 gene, which encodes a transcription-factor subunit [14].

Chemical compound and disease context of IFI44

• Mutagenesis along with recombinant technology using the baculovirus/insect cells expression system allowed us to define the function of the two structural motifs of the C-terminal moiety of p44: mutations within the C4 zinc finger motif (residues 291-308) prevent incorporation of the p62 subunit within the core TFIIH [15].
• Furthermore, it was observed that bromocriptine produced a time-dependent increase in the phosphorylation (activation) of p44/42 MAPK, which was blocked by domperidone, pertussis toxin, or PD 98059 [16].
• Further investigations of MIP-3alpha-induced signal transduction revealed time- and dose-dependent, partially pertussis toxin-dependent, increases in phosphorylation of the p42/p44 mitogen-activated protein kinases (MAPK) that occurred at 10- to 100-fold lower concentrations, and that were linked to a phosphoinositide 3-kinase pathway [17].
• Using PR-transfected breast cancer cells MDA-MB-231, this report describes the similarities and differences between progesterone- and RU486-mediated effects on cell growth, cell differentiation and, at the molecular level, on the activation of p44/p42 MAP kinases (MAPK) [18].
• Tamoxifen citrate also stimulated cell growth, associated with increased phosphorylation of p44/42 MAPK and expression of c-myc, indicating that tamoxifen has agonist effects on angiomyolipoma cells [19].

Biological context of IFI44

• The human p44 gene spans approximately 14 kbp of DNA and consists of nine exons separated by eight introns [1].
• Ca(2+) ionophore A23187 increases nuclear localization of PTEN and decreases phosphorylation of nuclear p44/42 [20].
• These studies support a role for inactivation of signaling through the p44/42 MAPK pathway in proteasome inhibitor-mediated apoptosis [21].
• Basic calcium phosphate crystals activate p44/42 MAPK signal transduction pathway via protein kinase Cmicro in human fibroblasts [22].
• Additionally, activation of different signal transduction pathways in C. pneumoniae-infected endothelial cells was shown: protein tyrosine phosphorylation, up-regulation of phosphorylated p42/p44 mitogen-activated protein kinase, and NF-kappaB activation/translocation occurred within 10-15 min [23].

Anatomical context of IFI44

• A hepatitis-C-associated microtubular aggregate protein, referred to as p44, has been identified as a cytoplasmic antigen in the hepatocytes of chimpanzees infected with hepatitis C virus [1].
• LFA-1 signaling through p44/42 is coupled to perforin degranulation in CD56+CD8+ natural killer cells [24].
• We and others have shown that the binding of SDF-1alpha to CXCR4 activates phosphatidylinositol-3 kinase (PI-3 kinase), p44/42 mitogen-associated protein kinase, and the transcription factor nuclear factor-kappaB, and it also enhances the tyrosine phosphorylation and association of proteins involved in the formation of focal adhesions [25].
• These results implicate p42mapk and p44 as important signal transducing molecules in myeloid cells, and it is likely that these kinases play a role as part of a sequential "kinase cascade" linking growth factor receptors to mitogenesis and other cellular responses [26].
• Lactosylceramide stimulates Ras-GTP loading, kinases (MEK, Raf), p44 mitogen-activated protein kinase, and c-fos expression in human aortic smooth muscle cells [27].

Associations of IFI44 with chemical compounds

• The site(s) of phosphorylation is identified as a serine residue(s) located in the hydrophilic carboxy terminus of the p44 chain [28].
• Purified, detergent-soluble HLA antigens (p44,12) are composed of a glycoprotein of molecular weight 44,000 (p44) and a peptide of molecular weight 12,000 (p12), beta2-microglobulin [29].
• In a previous study, we demonstrated that sodium salicylate (NaSal) selectively inhibits tumor necrosis factor (TNF)-induced activation of the p42 and p44 mitogen-activated protein kinases (MAPKs) (known as extracellular signal-regulated kinases) [30].
• Also, in AGER1 cells, AGE-induced H(2)O(2) formation and AGE- or S100-induced p44/p42 phosphorylation were suppressed, and these effects were restored by R1 siRNA [31].
• In contrast, guanosine 5'-[gamma-thio]triphosphate had no effect on the binding of IL-8 to p44 solubilized by digitonin [32].

Other interactions of IFI44

• The current study shows that small interfering RNA-mediated MVP silencing decreases the nuclear localization of PTEN and increases phosphorylation of nuclear p44/42 [20].
• This was followed by the downstream activation of p44/p42 mitogen-activated protein kinase (MAPK) over 15-20 min [33].
• Results: There were seven single nucleotide polymorphisms selected from six candidate genes including adenosine deaminase-RNA-specific, caspase 5, interferon consensus sequence binding protein 1, interferon-induced protein 44, phosphoinositide-3-kinase catalytic gamma polypeptide and transporter 2 ATP-binding cassette subfamily B genes [34].

Analytical, diagnostic and therapeutic context of IFI44

• Northern-blot analysis revealed that the human p44 gene is inducible by interferon-alpha/beta, but not by interferon-gamma [1].
• Microtubule-associated protein (MAP) kinase (p44) was Tyr-phosphorylated on immunoblotting and had increased activity in the immune-complex kinase assay [35].
• The phosphate group is attached to HLA-A and -B heavy chain (p44) as identified by immunoprecipitation with anti-beta2-microglobulin IgG, sodium dodecyl sulfate/polyacrylamide gel electrophoresis, isoelectric focusing, and susceptibility to limited proteolysis by papain and trypsin [28].
• The Src Homology 2 Domain-Containing Leukocyte Protein of 76-kDa Adaptor Links Integrin Ligation with p44/42 MAPK Phosphorylation and Podosome Distribution in Murine Dendritic Cells [36].
• Adhesion to laminin-1 mediated by the alpha6Abeta1 integrin triggered activation of a substantial fraction of total p42 and p44 MAP kinases as assessed using a mobility shift assay, immunoblot analysis with a phosphospecific MAP kinase antibody, and an immune complex kinase assay [37].

References