Disease relevance of Isgf3g

• Although p48 is the most conserved subunit of mammalian DNA polymerase alpha-primase (pol-prim), the polypeptide is the major species-specific factor for mouse polyomavirus (PyV) DNA replication [1].
• Increased expression of hypoxia-inducible factor-1alpha, p48, and the Notch signaling cascade during acute pancreatitis in mice [2].

High impact information on Isgf3g

• We show that the protooncogene Myc regulates the expression of p48 through the element CACGTG [3].
• We have identified a novel IFN-gamma-activated response element in the p48 gene promoter [4].
• Mutations in this motif abolish Myc-inducibility of the reporter genes carrying p48 promoter elements [3].
• Taken together these data suggest that p48 may function as an anti-stress cell survival factor [3].
• WD repeats of the p48 subunit of chicken chromatin assembly factor-1 required for in vitro interaction with chicken histone deacetylase-2 [5].

Biological context of Isgf3g

• Furthermore, the locus of the ISGF3 gamma gene, designated as Isgf3g, was mapped to distal mouse chromosome 14 by linkage analysis using an intersubspecific backcross typing panel [6].
• RESULTS: Primary cells from mice with a targeted disruption of the p48 gene show severe defects in virus-induced IFN-alpha/beta gene expression [7].
• To determine the functions of these splice variants in intact cells, we expressed a transgene encoding either a truncated form of murine arrestin (mArr(1-369), or m44) or the long (p48) isoform in mouse rods lacking endogenous arrestin (Arr-/-) [8].
• Suction electrode recordings from individual rods indicated that the expression of either m44 or p48 splice variants could restore normal kinetics to Arr-/- dim flash responses, indicating that both isoforms can bind to and quench phosphorylated rhodopsin rapidly [8].

Anatomical context of Isgf3g

• Fibroblasts and terminally differentiated myocytes of the rat heart display equally efficient GGR of 6-4PP but poor repair of CPD due to the absence of p48 expression [9].
• In the p48-deficient mice, the physiologic production of 2'5'OAS localized in the following cells was severely impaired: hepatocytes, Kupffer cells, splenocytes, epithelium of the large intestine, oviduct, and uterus, and neurons and glial cells in both the telencephalon and cerebellum [10].
• However, the production of 2'5'OAS in oocytes was not affected in the p48-deficient mice, indicating that oocyte 2'5'OAS is produced through a p48-independent pathway [10].
• Bovine rod photoreceptors express two splice variants of visual arrestin (p44 and p48) that display different affinities for the GPCR rhodopsin [8].

Associations of Isgf3g with chemical compounds

• More precisely, the nonconserved phenylalanine 262 of mouse p48 is crucial for this activity, and pol-prim with mutant p48, h-S262F, supports PyV DNA replication in vitro [1].
• Production of immunoreactive 2',5'-oligoadenylate synthetase in p48-deficient mice [10].

Other interactions of Isgf3g

• The interferon-stimulated gene factor 3 (ISGF3) transcription factor has been extensively studied in the context of the type I interferon (IFN-alpha/beta)-mediated antiviral response; it consists of the major DNA-binding component p48, and the signal transducers and activators of transcription (Stat)1 and Stat2 [11].
• Replacing the diverged amino acids in IRF-1 with the corresponding sequence of p48/IRF-9 resulted in a loss of inhibitory activity within IRF-1 [12].
• In this investigation, we show that the gene encoding p48, a subunit of transcription factor ISGF3, is transcriptionally induced by interferon gamma (IFN-gamma) [4].
• In cells lacking p48, an essential component of IFN stimulated gene factor 3 (ISGF3), ectopic expression of IRF-7 but not IRF-3 can rescue the deficiency to induce IFN-alpha genes [13].

Analytical, diagnostic and therapeutic context of Isgf3g

• Here, we examined the role of p48 (ISGF3gamma), a component of IFN-stimulated gene factor 3 (ISGF3), in the physiologic production of 2'5'OAS using p48-deficient mice generated by gene targeting [10].

References