Disease relevance of ACF

• In the short-term study, the effects of silymarin on the development of AOM-induced colonic ACF, being putative precursor lesions for colonic adenocarcinoma, were assayed to predict the modifying effects of dietary silymarin on colon tumorigenesis [1].
• Supranutritional amounts of Se supplied as high Se broccoli significantly decreased (P: < 0.05) the incidence of aberrant crypts (AC) and aberrant crypt foci (ACF; preneoplastic lesions indicative of colon cancer) compared with other dietary treatments [2].
• Identification of a novel transcription factor, ACF, in cultured avian fibroblast cells that interacts with a Marek's disease virus late gene promoter [3].
• Precursor lesions in the GIT include flat dysplasias, adenomas, dysplasia superimposed on nonneoplastic polyps, endocrine cell dysplasia, ACF, and condyloma accuminatum [4].
• ACF is possibly putative microadenoma that might be the precursor of adenoma [5].

High impact information on ACF

• Dynamics of ATP-dependent chromatin assembly by ACF [6].
• By using a purified ACF-dependent system for chromatin assembly, we found that ACF hydrolyses about 2#150;4 molecules of ATP per base pair in the assembly of nucleosomes [6].
• We have used a purified recombinant chromatin assembly system, including ACF (Acf-1 + ISWI) and NAP-1, to examine the role of histone acetylation in ATP-dependent chromatin remodeling [7].
• Order-of-addition experiments indicate that prior activator-meditated, ATP-dependent chromatin remodeling by ACF is required for the acetylation of nucleosomal histones by p300 [7].
• The "innocent colon" and K-ras mutation--guilty by (ACF) association [8]?

Chemical compound and disease context of ACF

• METHODS: Thirty-two patients with metastatic adenocarcinoma of the stomach, gastroesophageal junction, or esophagus were treated with cisplatin 60 mg/m2 and doxorubicin 30 mg/m2 repeated every 21 days, in combination with infusional 5-fluorouracil 200 mg/m2/day (ACF) [9].
• The use of the AOM-induced ACF assay to screen agents for the ability to prevent colon tumors would appear to result in false positive responses including agents (2-CPR and quercetin) that actually promote colon cancer [10].

Biological context of ACF

• Experiments using recombinant proteins demonstrate that GRY-RBP binds to ACF and inhibits both the binding of ACF to apoB RNA and C to U RNA editing [11].
• The APOBEC1 nuclear export signal is involved in the export of ACF and the edited apoB mRNA together, to the site of translation [12].
• Based on deletion mutagenesis, the RRMs in ACF are necessary but not sufficient for binding to apo-B mRNA [13].
• This complex contains apobec-1, the catalytic subunit, and apobec-1 complementation factor (ACF), the RNA-binding subunit that binds to the mooring sequence [13].
• The ACF gene spans approximately 80 kb and contains 15 exons, three of which are non-coding [14].

Anatomical context of ACF

• In both instances, the pattern of alternative splicing and overall abundance of ACF mRNA was relatively constant during development in both liver and small intestine [14].
• In order to examine the role of ACF mRNA expression in the regulation of apo B mRNA editing, we examined a panel of fetal intestinal and hepatic mRNAs as well as RNA from an intestinal cell line [14].
• Overexpression of these SR proteins in liver cells demonstrated that alternative splicing of a minigene-derived transcript to express ACF65 was enhanced 6-fold by SRp40 [15].
• The aim of the present study was to evaluate the intracellular ultrastructural distribution of beta-catenin and APC proteins in epithelial cells of normal colorectal mucosa, aberrant crypt foci (ACF, an early premalignant lesion) and cancer [16].
• Within a thin section, a significant amount of total cellular p66/ACF was cytoplasmic, with a concentration at the outer surface of the endoplasmic reticulum [17].

Associations of ACF with chemical compounds

• ACF relocates to the cytoplasm after actinomycin D treatment, an effect blocked by the CRM1 inhibitor leptomycin B [18].
• Our results support a model of the editing enzyme in which ACF binds to the mooring sequence in apo-B mRNA and docks apobec-1 to deaminate its target cytidine [19].
• Apobec1 is regulated by ACF (Apobec1 complementation factor) and hnRNPQ, which contains an N-terminal "acidic domain" (AcD) of unknown function, three RNA recognition motifs, and an Arg/Gly-rich region [20].
• When apoB mRNA editing was stimulated in rat primary hepatocytes with ethanol or insulin, the abundance of p66/ACF in the nucleus markedly increased [17].
• Foci of aberrant crypts (ACF) have been observed on the unsectioned, methylene blue-stained mucosal surface of the human colon [21].

Physical interactions of ACF

• The atypical APOBEC1 nuclear localization signal is involved in RNA binding and is used to import ACF into the nucleus as cargo [12].

Regulatory relationships of ACF

• Here we report that the nuclear protein nucleolin possesses a histone chaperone activity and that this factor greatly enhances the activity of the chromatin remodeling machineries SWI/SNF and ACF [22].

Other interactions of ACF

• ACF binds to the protein carrier, transportin 2 in vivo, and colocalizes to the nucleus as determined by confocal microscopy [18].
• We demonstrate that the APOBEC1-ACF holoenzyme mediates a multifunctional cycle [12].
• The C to U editing of apolipoprotein B (apoB) mRNA is mediated by a minimal complex composed of an RNA-binding cytidine deaminase (APOBEC1) and a complementing specificity factor (ACF) [12].
• Antisense CUGBP2 knockout increased endogenous apoB RNA editing, whereas antisense knockout of either apobec-1 or ACF expression eliminated apoB RNA editing, establishing the absolute requirement of these components of the core enzyme [23].
• ACF/ASP is novel, and emerging information reveals interesting clues to its role in the apolipoprotein B RNA editing enzyme complex [24].

Analytical, diagnostic and therapeutic context of ACF

• By UV cross-linking and immunoprecipitation, we show that ACF binds to apo-B mRNA in vitro and in vivo [19].
• In this first study of human ACF with this approach, the finding of altered DNA fingerprints in these microscopic lesions suggests that genomic instability can occur very early in human colon tumorigenesis [25].
• The PCR products, separated by PAGE and viewed after silver staining, demonstrate altered fingerprints for 23.3% of the ACF and 95.7% of the cancers [25].
• Atomic force microscopy, however, suggests that NAP-1 alone fails to accomplish the formation of fine nucleosomal core particles, which are only formed in the presence of ACF [26].
• The equilibrium unfolding/refolding of apo-ACF II, holo-ACF II, and Tb(3+)-reconstituted ACF II in guanidine hydrochloride (GdnHCl) solutions was studied by following the fluorescence and circular dichroism (CD) [27].

References