Disease relevance of Nfib

• On both the WAP CoRE and the mouse mammary tumor virus long terminal repeat promoter, the NFI-B isoform preferentially activated gene transcription in cooperation with STAT5A and GR [1].
• 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 [2].
• 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 [3].
• 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 [4].
• The CTF for weeks 1-13 for MnCl2 ranged from 0 to 3.48; endosulfan LD50 and CLD50 values for a mixture of MnCl2 and endosulfan were higher than the expected values, indicating a greatly reduced toxicity of a mixture, when given either in a single dose or repeated doses [5].

High impact information on Nfib

• The similarity in brain defects in Nfia- and Nfib-deficient animals suggests that these two genes may cooperate in late fetal forebrain development, while Nfib is essential for late fetal lung maturation and development of the pons [6].
• In addition, loss of Nfib results in defects in basilar pons formation and hippocampus development that are not seen in Nfia-deficient mice [6].
• Essential role for NFI-C/CTF transcription-replication factor in tooth root development [7].
• The B subunit of the CCAAT box binding transcription factor complex (CBF/NF-Y) is essential for early mouse development and cell proliferation [8].
• Since DAPT treatment resulted in increased beta2-CTF levels, we also tested whether beta2-CTFs or beta2-ICDs would directly affect cell migration by overexpressing recombinant proteins [9].

Biological context of Nfib

• The four genes exhibit unique but overlapping patterns of expression during embryonic development, with high level expression of NFI-A, NFI-B, and NFI-X transcripts in neocortex and extensive expression of the four genes in muscle, connective tissue, liver, and other organ systems [10].
• In the present study, we isolated multiple cDNAs encoding a family of NFI, NFI-B, from mouse brain cDNA libraries [11].
• Furthermore, we demonstrated by transfection experiments that NFI-B activated transcription from transfected MBP promoter in neuronal/glial NG108-15 cells [11].
• It is most likely that this lactation/involution switch in NF1 factors represents a change in expression of NF1 C (CTF/NF1) proteins [12].
• 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 [13].

Anatomical context of Nfib

• Here we show that Nfib-deficient mice possess unique defects in lung maturation and exhibit callosal agenesis and forebrain defects that are similar to, but more severe than, those seen in Nfia-deficient animals [6].
• No mutations were found in these genes; however, unexpectedly, increased expression of the transcription factor NFI-B was detected in granulocytes and CD34(+) cells in PV with 9pLOH [14].
• Here, we report that binding sites for the transcription factor CTF/NF-I mediate antagonistic TGF-beta and TNF-alpha transcriptional regulation in NIH3T3 fibroblasts [15].
• 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 [4].
• In addition, another transcription factor, CTF/NF-1, binds the proximal promoter immediately downstream of this region and its mutation decreases transcription in NIH-3T3 cells [16].

Associations of Nfib with chemical compounds

• Within the distal hypersensitive region several binding sites for members of the CTF/NFI family of transcription factors were identified using in vitro DNase I and dimethyl sulfate interference footprinting and electrophoretic mobility shift assays [17].
• PS1 and PS2 are polytopic membrane proteins that undergo endoproteolytic cleavage to generate stable NH2- and COOH-terminal derivatives (NTF and CTF, respectively) [2].
• Experiments using metabolic labeling and cycloheximide treatment revealed that zinc increased PS1-CTF by elevating the de novo synthesis of PS1 [18].
• METHODS: Male C57BL/6 mice were divided into 4 groups: (1) control mice fed ad libitum (Control); (2) tumor-bearing mice fed ad libitum (TB); (3) control mice receiving tube feeding (CTF); and (4) tumor-bearing mice receiving tube feeding (TBTF) [19].
• We show that aspartate-mutant holoprotein presenilins are not incorporated into the high molecular weight, NTF/CTF-containing complexes [20].

Other interactions of Nfib

• The four NFI gene products studied differ in their ability to activate expression of the NFI-dependent MMTV promoter, with the NFI-B protein being most active and the NFI-A protein being least active [10].
• All four NFI genes are expressed in embryonic mouse brain, with Nfia, Nfib, and Nfix being expressed highly in developing cortex (Chaudhry et al., 1997) [21].

Analytical, diagnostic and therapeutic context of Nfib

• We also showed that PS-1 NTF but not CTF forms strong high molecular weight aggregates in SDS-PAGE [22].
• EXPERIMENTAL DESIGN: Polymeric microspheres made of poly(lactic-co-glycolic acid) (PLGA) were loaded with very low amounts of PEX and PF-4/CTF [4].

References