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Gene Review

A1CF  -  APOBEC1 complementation factor

Homo sapiens

Synonyms: ACF, ACF64, ACF65, APOBEC1-stimulating protein, APOBEC1CF, ...
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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


Chemical compound and disease context of ACF


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


  1. Silymarin, a naturally occurring polyphenolic antioxidant flavonoid, inhibits azoxymethane-induced colon carcinogenesis in male F344 rats. Kohno, H., Tanaka, T., Kawabata, K., Hirose, Y., Sugie, S., Tsuda, H., Mori, H. Int. J. Cancer (2002) [Pubmed]
  2. Selenium from high selenium broccoli protects rats from colon cancer. Finley, J.W., Davis, C.D., Feng, Y. J. Nutr. (2000) [Pubmed]
  3. Identification of a novel transcription factor, ACF, in cultured avian fibroblast cells that interacts with a Marek's disease virus late gene promoter. Coussens, P.M., Tieber, V.L., Mehigh, C.S., Marcus, M. Virology (1991) [Pubmed]
  4. Histologic precursors of gastrointestinal tract malignancy. Haber, M.M. Gastroenterol. Clin. North Am. (2002) [Pubmed]
  5. APC and K-ras gene mutation in aberrant crypt foci of human colon. Yuan, P., Sun, M.H., Zhang, J.S., Zhu, X.Z., Shi, D.R. World J. Gastroenterol. (2001) [Pubmed]
  6. Dynamics of ATP-dependent chromatin assembly by ACF. Fyodorov, D.V., Kadonaga, J.T. Nature (2002) [Pubmed]
  7. p300-mediated acetylation facilitates the transfer of histone H2A-H2B dimers from nucleosomes to a histone chaperone. Ito, T., Ikehara, T., Nakagawa, T., Kraus, W.L., Muramatsu, M. Genes Dev. (2000) [Pubmed]
  8. The "innocent colon" and K-ras mutation--guilty by (ACF) association? Zalewska, I., Tobi, M. Gastroenterology (2003) [Pubmed]
  9. A phase II study of doxorubicin, cisplatin, and 5-fluorouracil in patients with advanced adenocarcinoma of the stomach or esophagus. Kulke, M.H., Wu, B., Clark, J.W., Enzinger, P.C., Lynch, T.J., Vincitore, M., Michelini, A., Fuchs, C.S. Cancer Invest. (2006) [Pubmed]
  10. Prevention of colon cancer and modulation of aberrant crypt foci, cell proliferation, and apoptosis by retinoids and NSAIDs. Pereira, M.A. Adv. Exp. Med. Biol. (1999) [Pubmed]
  11. Identification of GRY-RBP as an apolipoprotein B RNA-binding protein that interacts with both apobec-1 and apobec-1 complementation factor to modulate C to U editing. Blanc, V., Navaratnam, N., Henderson, J.O., Anant, S., Kennedy, S., Jarmuz, A., Scott, J., Davidson, N.O. J. Biol. Chem. (2001) [Pubmed]
  12. The apolipoprotein B mRNA editing complex performs a multifunctional cycle and suppresses nonsense-mediated decay. Chester, A., Somasekaram, A., Tzimina, M., Jarmuz, A., Gisbourne, J., O'Keefe, R., Scott, J., Navaratnam, N. EMBO J. (2003) [Pubmed]
  13. Identification of domains in apobec-1 complementation factor required for RNA binding and apolipoprotein-B mRNA editing. Mehta, A., Driscoll, D.M. RNA (2002) [Pubmed]
  14. Isolation, characterization and developmental regulation of the human apobec-1 complementation factor (ACF) gene. Henderson, J.O., Blanc, V., Davidson, N.O. Biochim. Biophys. Acta (2001) [Pubmed]
  15. Two proteins essential for apolipoprotein B mRNA editing are expressed from a single gene through alternative splicing. Dance, G.S., Sowden, M.P., Cartegni, L., Cooper, E., Krainer, A.R., Smith, H.C. J. Biol. Chem. (2002) [Pubmed]
  16. Subcellular localization of beta-catenin and APC proteins in colorectal preneoplastic and neoplastic lesions. Sena, P., Saviano, M., Monni, S., Losi, L., Roncucci, L., Marzona, L., Pol, A.D. Cancer Lett. (2006) [Pubmed]
  17. The editosome for cytidine to uridine mRNA editing has a native complexity of 27S: identification of intracellular domains containing active and inactive editing factors. Sowden, M.P., Ballatori, N., Jensen, K.L., Reed, L.H., Smith, H.C. J. Cell. Sci. (2002) [Pubmed]
  18. A novel nuclear localization signal in the auxiliary domain of apobec-1 complementation factor regulates nucleocytoplasmic import and shuttling. Blanc, V., Kennedy, S., Davidson, N.O. J. Biol. Chem. (2003) [Pubmed]
  19. Molecular cloning of apobec-1 complementation factor, a novel RNA-binding protein involved in the editing of apolipoprotein B mRNA. Mehta, A., Kinter, M.T., Sherman, N.E., Driscoll, D.M. Mol. Cell. Biol. (2000) [Pubmed]
  20. The acidic domain of hnRNPQ (NSAP1) has structural similarity to Barstar and binds to Apobec1. Quaresma, A.J., Oyama, S., Barbosa, J.A., Kobarg, J. Biochem. Biophys. Res. Commun. (2006) [Pubmed]
  21. Cell kinetic evaluation of human colonic aberrant crypts. (Colorectal Cancer Study Group of the University of Modena and the Health Care District 16, Modena, Italy). Roncucci, L., Pedroni, M., Fante, R., Di Gregorio, C., Ponz de Leon, M. Cancer Res. (1993) [Pubmed]
  22. Nucleolin is a histone chaperone with FACT-like activity and assists remodeling of nucleosomes. Angelov, D., Bondarenko, V.A., Almagro, S., Menoni, H., Mongélard, F., Hans, F., Mietton, F., Studitsky, V.M., Hamiche, A., Dimitrov, S., Bouvet, P. EMBO J. (2006) [Pubmed]
  23. Novel role for RNA-binding protein CUGBP2 in mammalian RNA editing. CUGBP2 modulates C to U editing of apolipoprotein B mRNA by interacting with apobec-1 and ACF, the apobec-1 complementation factor. Anant, S., Henderson, J.O., Mukhopadhyay, D., Navaratnam, N., Kennedy, S., Min, J., Davidson, N.O. J. Biol. Chem. (2001) [Pubmed]
  24. Molecular mechanisms of apolipoprotein B mRNA editing. Anant, S., Davidson, N.O. Curr. Opin. Lipidol. (2001) [Pubmed]
  25. DNA alterations in human aberrant crypt foci and colon cancers by random primed polymerase chain reaction. Luo, L., Li, B., Pretlow, T.P. Cancer Res. (2003) [Pubmed]
  26. Multistep chromatin assembly on supercoiled plasmid DNA by nucleosome assembly protein-1 and ATP-utilizing chromatin assembly and remodeling factor. Nakagawa, T., Bulger, M., Muramatsu, M., Ito, T. J. Biol. Chem. (2001) [Pubmed]
  27. Metal ion-induced stabilization and refolding of anticoagulation factor II from the venom of Agkistrodon acutus. Xu, X., Liu, Q., Xie, Y. Biochemistry (2002) [Pubmed]
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