Disease relevance of Btg1

• Of 35 genes highly expressed in inner medulla, 6 genes such as; B-cell translocation gene protein (BTG), myc-basic motif homologue, gelsolin, cell surface glycoprotein, laminin beta2, and tubulo-interstitial nephritis antigen, were also expressed highly in HT cells [1].

High impact information on Btg1

• The expression of BTG1 was synergistically enhanced by LPS and IFN-gamma in BV-2 mouse microglial cells as well as in primary microglia cultures [2].
• Role of antiproliferative B cell translocation gene-1 as an apoptotic sensitizer in activation-induced cell death of brain microglia [2].
• Nucleotide sequencing reveals that the Tob protein is a 45 kDa protein that does not contain either SH2 (Src Homology 2) or SH3 domain but is homologous to the previously characterized anti-proliferative gene product BTG-1 at its amino-terminal half [3].
• In view of the impairment of immune function by protein restriction that causes SD, this study investigated whether SD or other oxidative stress inhibits iNOS and cytokine expression and induces Btg-1 in macrophages and explored the causal relationship of Btg-1 induction and repression of the genes [4].
• Repression by oxidative stress of iNOS and cytokine gene induction in macrophages results from AP-1 and NF-kappaB inhibition mediated by B cell translocation gene-1 activation [4].

Biological context of Btg1

• Tetracycline-based conditional expression of BTG1 not only suppressed microglial proliferation but also increased the sensitivity of microglial cells to NO-induced apoptosis, suggesting a novel mechanism of cooperation between LPS and IFN-gamma in the induction of microglial apoptosis [2].
• Oxidative stress increased Btg-1 mRNA [4].
• Expression of Btg-1 inhibited lipopolysaccharide-inducible AP-1 and NF-kappaB activities, repressing transactivation of the target gene pGL-miNOS-1588 [4].
• Subsequently, the DNA sequence of a differentially expressed cDNA clone was determined and the cDNA was identified as B-cell translocation gene-1 (BTG1), a recently cloned antiproliferative gene [5].
• The putative human and mouse BTG1 proteins are 100% identical; the chicken BTG1 cDNA contains an open reading frame of 170 amino acids with a 91% identity to its human and murine counterparts [6].

Anatomical context of Btg1

• SD-induced oxidative stress activated Btg-1 in macrophages, as evidenced by nuclear translocation of endogenous or green fluorescent protein-tagged Btg-1, which localized in the cytoplasm in the resting state [4].
• Previously, we reported that oxidative stress caused by sulfur amino acid deficiency (SD) induces B cell translocation gene-1 (Btg-1), which belongs to the Apro family, in hepatocytes [4].
• A member of the B cell translocation gene/transducer of ErbB-2 (BTG/TOB) family of anti-proliferative proteins was identified as a key mediator of the quiescent state in peripheral anergic and unstimulated T cells [7].

Associations of Btg1 with chemical compounds

• Enhancement of B-cell translocation gene-1 expression by prostaglandin E2 in macrophages and the relationship to proliferation [5].
• PGE1 and platelet-activating factor, but not leukotrienes B4, and C4, or lipopolysaccharide, also enhanced BTG1 expression [5].
• Furthermore, this effect ws mimicked by dibutyryl cAMP which indicated the involvement of elevated cAMP in the PGE2-mediated enhancement of BTG1 [5].

Other interactions of Btg1

• TIS1 encodes a protein of unknown function with strong sequence similarity to BTG1, a proposed "anti-proliferative gene" (Rouault JP, Rimokh R, Tessa C, et al., EMBO J 11:1663-1670, 1992) [8].

Analytical, diagnostic and therapeutic context of Btg1

• We cloned zebrafish btg-b, a member of the BTG1/2 subfamily, using in situ hybridization screening [9].
• Sequence analysis reveals that the BTG1 anti-proliferative gene is conserved throughout evolution in its coding and 3' non-coding regions [6].

References