Disease relevance of NFIX

• Binding sites for CTF in the human Ha-ras and alpha-globin promoters were highly homologous to sequences recognized by nuclear factor I (NF-I), a cellular DNA-binding protein that is required for the initiation of adenovirus DNA replication in vitro [1].
• A mammary cell-specific enhancer in mouse mammary tumor virus DNA is composed of multiple regulatory elements including binding sites for CTF/NFI and a novel transcription factor, mammary cell-activating factor [2].
• JC virus susceptibility correlated with significantly higher expression of the NFI-X transcription factor in astrocytes than in neurons [3].
• In the present report, we examine the disposition of PS NTF and CTF assemblies in stable mouse N2a neuroblastoma cell lines expressing human PS polypeptides [4].
• A single local s.c. injection of PLGA microspheres loaded with low amounts of PEX or PF-4/CTF resulted in an 88% and 95% reduction in glioma tumor volume 30 days post-treatment [5].

High impact information on NFIX

• We studied a model viral chromosome containing a single binding site for the cellular transcriptional activator, nuclear factor I (NF-I/CTF), located adjacent to the replication origin [6].
• CTF and NF-I were found to be indistinguishable in polypeptide composition, DNA-binding properties, immunological cross-reactivity, and in vitro stimulation of DNA replication and transcription initiation [1].
• Together, these two domains constitute the full NFI-X transactivation potential [7].
• Furthermore, transfection of an NFI-X expression vector into progenitor-derived neuronal cells before infection resulted in viral protein production [3].
• In addition, we found, using isoform-specific siRNAs, that NFI-X regulates the astrocyte-specific expression of ACT and GFAP [8].

Biological context of NFIX

• This property, combined with the differential expression of NFI-X, can achieve cell-type specificity of NFI dependent promoters and enhancers [9].
• Cloning and functional analysis of spliced isoforms of human nuclear factor I-X: interference with transcriptional activation by NFI/CTF in a cell-type specific manner [9].
• The activity of the nuclear factor I/CCAAT transcription factor (NFI/CTF) is negatively regulated by oxidative stress [10].
• In this study, we determined the genomic organization and nucleotide sequences of the exon/intron boundaries of the rat Nfib, Nfic and Nfix genes in silico [11].
• The adenovirus origin of DNA replication is located within the terminal 51 bp of the viral genome and contains three recognizable domains: the minimal origin or "core" and binding sites for the cellular transcription factors NFI (CTF) and NFIII (oct-1, OTF-I) [12].

Anatomical context of NFIX

• Electrophoretic mobility shift assays revealed that transcription factors of the hepatocyte nuclear factor-3 (HNF-3) and nuclear factor-I (NFI/CTF) families were able to bind to this region in a sequence-specific manner [13].
• In contrast, fibroblasts, where the enhancer is inactive, express high levels of NFI from the NFI-X gene [9].
• The TGGCA-binding protein from HeLa cells appears to be identical to nuclear factor I described by others, which stimulates initiation of adenovirus DNA replication in vitro [14].
• RESULTS: PEX and PF-4/CTF released in vitro from PLGA microspheres were biologically active and significantly inhibited the proliferation of human umbilical vein endothelial cells, bovine capillary endothelial cells, and U87-MG cells [5].

Associations of NFIX with chemical compounds

• The addition of relatively high (millimolar) H(2)O(2) concentrations inactivates cellular NFI DNA-binding activity whereas lower concentrations can repress NFI/CTF transactivating function [10].
• The Nuclear Factor I (NFI) family of site-specific DNA-binding proteins (also known as CTF or CAAT box transcription factor) functions both in viral DNA replication and in the regulation of gene expression [15].
• PS1 and PS2 are polytopic membrane proteins that undergo endoproteolytic cleavage to generate stable NH2- and COOH-terminal derivatives (NTF and CTF, respectively) [4].
• We show that aspartate-mutant holoprotein presenilins are not incorporated into the high molecular weight, NTF/CTF-containing complexes [16].

Other interactions of NFIX

• We propose that NFI-X cooperates with AP-1 by an unknown mechanism in astrocytes, which results in the expression of a subset of astrocyte-specific genes [8].

Analytical, diagnostic and therapeutic context of NFIX

• Real-time reverse transcriptase-polymerase chain reaction (RT-PCR) assays have demonstrated that NFI-X is the predominant NFI mRNA expressed in As4.1 cells [17].
• EXPERIMENTAL DESIGN: Polymeric microspheres made of poly(lactic-co-glycolic acid) (PLGA) were loaded with very low amounts of PEX and PF-4/CTF [5].
• The insertion of a chest tube was required in only one (2%) procedure using the CTF technique, while this was needed in four (10%) using the conventional technique [18].

References