fanconi anemia complementation group f protein

Summary

Summary: A Fanconi anemia complementation group protein. It is an essential component of a nuclear core complex that protects the GENOME against CHROMOSOMAL INSTABILITY. It interacts directly with FANCG PROTEIN and helps stabilize a complex with FANCA PROTEIN and FANCC PROTEIN.

Top Publications

  1. de Winter J, van Der Weel L, de Groot J, Stone S, Waisfisz Q, Arwert F, et al. The Fanconi anemia protein FANCF forms a nuclear complex with FANCA, FANCC and FANCG. Hum Mol Genet. 2000;9:2665-74 pubmed
    ..Our results, along with published data, culminate in a model in which a multi-protein FA complex serves a nuclear function to maintain genomic integrity. ..
  2. Lim S, Smith P, Syed N, Coens C, Wong H, van der Burg M, et al. Promoter hypermethylation of FANCF and outcome in advanced ovarian cancer. Br J Cancer. 2008;98:1452-6 pubmed publisher
    ..There was no association with overall survival. This study does not support methylation-dependent silencing of FANCF as a mechanism of sensitisation to platinum-based chemotherapy in ovarian cancer...
  3. Wang Z, Li M, Lu S, Zhang Y, Wang H. Promoter hypermethylation of FANCF plays an important role in the occurrence of ovarian cancer through disrupting Fanconi anemia-BRCA pathway. Cancer Biol Ther. 2006;5:256-60 pubmed
    ..Methylation-induced inactivation of FANCF plays an important role in the occurrence of ovarian cancers via disrupting the FA-BRCA pathway. ..
  4. Koul S, McKiernan J, Narayan G, Houldsworth J, Bacik J, Dobrzynski D, et al. Role of promoter hypermethylation in Cisplatin treatment response of male germ cell tumors. Mol Cancer. 2004;3:16 pubmed
    ..These results also implicate defects in epigenetic pathways that regulate gene transcription in cisplatin resistant GCT. ..
  5. Narayan G, Arias Pulido H, Nandula S, Basso K, Sugirtharaj D, Vargas H, et al. Promoter hypermethylation of FANCF: disruption of Fanconi Anemia-BRCA pathway in cervical cancer. Cancer Res. 2004;64:2994-7 pubmed
    ..Thus, these results have important implications in understanding the molecular basis of CC tumorigenesis and clinical management in designing targeted experimental therapeutic protocols. ..
  6. Tischkowitz M, Ameziane N, Waisfisz Q, de Winter J, Harris R, Taniguchi T, et al. Bi-allelic silencing of the Fanconi anaemia gene FANCF in acute myeloid leukaemia. Br J Haematol. 2003;123:469-71 pubmed
    ..As FANCF is localized in a hot-spot region for somatic hypermethylation (11p15), FANCF silencing might be an early step in sporadic carcinogenesis, including leukaemogenesis. ..
  7. Olopade O, Wei M. FANCF methylation contributes to chemoselectivity in ovarian cancer. Cancer Cell. 2003;3:417-20 pubmed
    ..Disruption of the pathway occurs de novo in ovarian cancers and may contribute to selective sensitivity to platinum salts. ..
  8. Medhurst A, Huber P, Waisfisz Q, de Winter J, Mathew C. Direct interactions of the five known Fanconi anaemia proteins suggest a common functional pathway. Hum Mol Genet. 2001;10:423-9 pubmed
    ..These proteins may act either as a multimeric complex or by sequential recruitment of subsets of the proteins in a common pathway that protects the genomic integrity of mammalian cells. ..
  9. Taniguchi T, Tischkowitz M, Ameziane N, Hodgson S, Mathew C, Joenje H, et al. Disruption of the Fanconi anemia-BRCA pathway in cisplatin-sensitive ovarian tumors. Nat Med. 2003;9:568-74 pubmed
    ..We propose a model for ovarian tumor progression in which the initial methylation of FANCF is followed by FANCF demethylation and ultimately results in cisplatin resistance. ..

More Information

Publications41

  1. Bagby G, Olson S. Cisplatin and the sensitive cell. Nat Med. 2003;9:513-4 pubmed
  2. Tumini E, Plevani P, Muzi Falconi M, Marini F. Physical and functional crosstalk between Fanconi anemia core components and the GINS replication complex. DNA Repair (Amst). 2011;10:149-58 pubmed publisher
    ..However, depletion of PSF2 is not sufficient to reduce monoubiquitylation of FANCD2 or its localization to nuclear foci following DNA damage. Our results suggest a novel crosstalk between DNA replication and the FA pathway. ..
  3. D Andrea A. The Fanconi Anemia/BRCA signaling pathway: disruption in cisplatin-sensitive ovarian cancers. Cell Cycle. 2003;2:290-2 pubmed
    ..The serial inactivation and reactivation of the FA/BRCA pathway has important implications for the diagnosis and treatment of ovarian cancers and related cancers. ..
  4. Chen C, Taniguchi T, D ANDREA A. The Fanconi anemia (FA) pathway confers glioma resistance to DNA alkylating agents. J Mol Med (Berl). 2007;85:497-509 pubmed
    ..The results presented in this paper underscore the complexity of cellular resistance to DNA alkylating agents and implicate the FA repair pathway as a determinant of this resistance. ..
  5. Kowal P, Gurtan A, Stuckert P, D Andrea A, Ellenberger T. Structural determinants of human FANCF protein that function in the assembly of a DNA damage signaling complex. J Biol Chem. 2007;282:2047-55 pubmed
    ..FANCF mutants bearing amino acid substitutions in this C-terminal surface fail to interact with other components of the FA complex, indicating that this surface is critical for the proper assembly of the FA core complex. ..
  6. Léveillé F, Blom E, Medhurst A, Bier P, Laghmani E, Johnson M, et al. The Fanconi anemia gene product FANCF is a flexible adaptor protein. J Biol Chem. 2004;279:39421-30 pubmed
    ..Our data demonstrate that FANCF acts as a flexible adaptor protein that plays a key role in the proper assembly of the FA core complex. ..
  7. Chen Q, Van der Sluis P, Boulware D, Hazlehurst L, Dalton W. The FA/BRCA pathway is involved in melphalan-induced DNA interstrand cross-link repair and accounts for melphalan resistance in multiple myeloma cells. Blood. 2005;106:698-705 pubmed
    ..These data show that enhanced DNA repair via the Fanconi anemia/BRCA pathway is involved in acquired melphalan resistance. Our findings provide for a new target to enhance response to DNA cross-linking agents in cancer treatment. ..
  8. Bakker S, van de Vrugt H, Visser J, Delzenne Goette E, van der Wal A, Berns M, et al. Fancf-deficient mice are prone to develop ovarian tumours. J Pathol. 2012;226:28-39 pubmed publisher
  9. Tokunaga E, Okada S, Kitao H, Shiotani S, Saeki H, Endo K, et al. Low incidence of methylation of the promoter region of the FANCF gene in Japanese primary breast cancer. Breast Cancer. 2011;18:120-3 pubmed publisher
    ..FANCF methylation is a rare event in Japanese primary invasive breast cancer. This suggests it is not involved in the pathogenesis of TNBC, and it could not be used as a predictor of cisplatin sensitivity in breast cancer. ..
  10. Swisher E, Gonzalez R, Taniguchi T, Garcia R, Walsh T, Goff B, et al. Methylation and protein expression of DNA repair genes: association with chemotherapy exposure and survival in sporadic ovarian and peritoneal carcinomas. Mol Cancer. 2009;8:48 pubmed publisher
    ..However, alterations in expression of these proteins after chemotherapy are not commonly mediated by promoter methylation, and other regulatory mechanisms are likely to contribute to these alterations. ..
  11. Wilson J, Yamamoto K, Marriott A, Hussain S, Sung P, Hoatlin M, et al. FANCG promotes formation of a newly identified protein complex containing BRCA2, FANCD2 and XRCC3. Oncogene. 2008;27:3641-52 pubmed publisher
    ..Our findings further define the intricate interface between FANC and HRR proteins in maintaining chromosome stability. ..
  12. Wei M, Xu J, Dignam J, Nanda R, Sveen L, Fackenthal J, et al. Estrogen receptor alpha, BRCA1, and FANCF promoter methylation occur in distinct subsets of sporadic breast cancers. Breast Cancer Res Treat. 2008;111:113-20 pubmed
    ..These data suggest that unlike FANCF, both ER and BRCA1 are specifically targeted for methylation in sporadic breast cancers, a phenomenon that should be explored for development of novel diagnostic and therapeutic approaches. ..
  13. Meyer S, White D, Will A, Eden T, Sim A, Brown R, et al. No evidence of significant silencing of Fanconi genes FANCF and FANCB or Nijmegen breakage syndrome gene NBS1 by DNA hyper-methylation in sporadic childhood leukaemia. Br J Haematol. 2006;134:61-3 pubmed
    ..This does not exclude very low levels of FANCF, FANCB or NBS1 methylation, but suggests other factors are responsible for chemo-sensitivity and chromosomal instability in sporadic childhood leukaemia. ..
  14. Meier D, Schindler D. Fanconi anemia core complex gene promoters harbor conserved transcription regulatory elements. PLoS ONE. 2011;6:e22911 pubmed publisher
    ..These results support a hypothesis based on the co-evolution of the FA core complex genes that was expanded to include their promoters. ..
  15. Turner N, Tutt A, Ashworth A. Hallmarks of 'BRCAness' in sporadic cancers. Nat Rev Cancer. 2004;4:814-9 pubmed publisher
    ..These common properties might have important implications for the clinical management of these cancers. ..
  16. Yamashita T, Nakahata T. Current knowledge on the pathophysiology of Fanconi anemia: from genes to phenotypes. Int J Hematol. 2001;74:33-41 pubmed
    ..Clarifying the molecular basis of this disease may provide new insights into the pathogenesis of bone marrow failure syndromes and myeloid malignancies. ..
  17. Parashar G, Parashar N, Capalash N. Curcumin causes promoter hypomethylation and increased expression of FANCF gene in SiHa cell line. Mol Cell Biochem. 2012;365:29-35 pubmed publisher
    ..Resveratrol was not found to be effective in causing reversal of promoter hypermethylation of FANCF gene when used at 20 lM for 4 days in SiHa cell line. ..
  18. He M, Sun H, Hao J, Li Y, Yu J, Yan Y, et al. RNA interference-mediated FANCF silencing sensitizes OVCAR3 ovarian cancer cells to adriamycin through increased adriamycin-induced apoptosis dependent on JNK activation. Oncol Rep. 2013;29:1721-9 pubmed publisher
    ..Collectively, we confirm that silencing of FANCF sensitizes OVCAR3 ovarian cancer cells to ADM, suggesting that FANCF may serve as a potential target for therapeutic strategies in the treatment of ovarian cancer. ..
  19. Croop J. Gene therapy for fanconi anemia. Curr Hematol Rep. 2003;2:335-40 pubmed
    ..Fanconi anemia represents a prototype disorder for gene therapy and highlights the difficulties in adapting this technology to human disease. ..
  20. Gordon S, Buchwald M. Fanconi anemia protein complex: mapping protein interactions in the yeast 2- and 3-hybrid systems. Blood. 2003;102:136-41 pubmed
    ..Direct interaction between FANCE and FANCD2 was also demonstrated in the yeast 2-hybrid system. This interaction involving an amino-terminal region of FANCD2 may provide a link between the FA protein complex and its downstream targets. ..
  21. Li Y, Zhao L, Sun H, Yu J, Li N, Liang J, et al. Gene silencing of FANCF potentiates the sensitivity to mitoxantrone through activation of JNK and p38 signal pathways in breast cancer cells. PLoS ONE. 2012;7:e44254 pubmed publisher
    ..Our findings indicate that FANCF shRNA potentiates the sensitivity of breast cancer cells to MX, suggesting that FANCF may be a potential target for therapeutic strategies for the treatment of breast tumors. ..
  22. de Winter J, Rooimans M, van Der Weel L, van Berkel C, Alon N, Bosnoyan Collins L, et al. The Fanconi anaemia gene FANCF encodes a novel protein with homology to ROM. Nat Genet. 2000;24:15-6 pubmed
  23. Ding J, Wang G, Shi W, Zhou H, Zhao E. Promoter Hypermethylation of FANCF and Susceptibility and Prognosis of Epithelial Ovarian Cancer. Reprod Sci. 2016;23:24-30 pubmed publisher
    ..CpG island methylation of FANCF gene promoter region is strongly associated with the susceptibility and clinicopathologic features of EOC. The FIGO staging and FANCF methylation are independent risk factors for EOC prognosis. ..
  24. Kusayanagi T, Tsukuda S, Shimura S, Manita D, Iwakiri K, Kamisuki S, et al. The antitumor agent doxorubicin binds to Fanconi anemia group F protein. Bioorg Med Chem. 2012;20:6248-55 pubmed publisher
    ..We observed that the monoubiquitination was inhibited by doxorubicin treatment. ..
  25. Saberwal G, Horvath E, Hu L, Zhu C, Hjort E, Eklund E. The interferon consensus sequence binding protein (ICSBP/IRF8) activates transcription of the FANCF gene during myeloid differentiation. J Biol Chem. 2009;284:33242-54 pubmed publisher
    ..Our studies suggest that ICSBP deficiency may be functionally important for accumulation of chromosomal abnormalities during disease progression in these myeloid malignancies. ..
  26. Lyakhovich A, Surralles J. Disruption of the Fanconi anemia/BRCA pathway in sporadic cancer. Cancer Lett. 2006;232:99-106 pubmed
    ..All this may serve as a platform for occurrence, development and treatment of sporadic cancers and therefore deserves to be in the focus of new research directions. ..
  27. Dhillon V, Shahid M, Husain S. CpG methylation of the FHIT, FANCF, cyclin-D2, BRCA2 and RUNX3 genes in Granulosa cell tumors (GCTs) of ovarian origin. Mol Cancer. 2004;3:33 pubmed
    ..These results may have implications in better understanding the underlying epigenetic mechanisms in GCT development, provide prognostic indicators, and identify important gene targets for treatment. ..
  28. Seal S, Barfoot R, Jayatilake H, Smith P, Renwick A, Bascombe L, et al. Evaluation of Fanconi Anemia genes in familial breast cancer predisposition. Cancer Res. 2003;63:8596-9 pubmed
    ..The results indicate that FA gene mutations, other than in BRCA2, are unlikely to be a frequent cause of highly penetrant breast cancer predisposition. ..
  29. Adachi D, Oda T, Yagasaki H, Nakasato K, Taniguchi T, D Andrea A, et al. Heterogeneous activation of the Fanconi anemia pathway by patient-derived FANCA mutants. Hum Mol Genet. 2002;11:3125-34 pubmed
    ..Reconstitution of the FA pathway by group II and III mutants closely correlated with cellular sensitivity to MMC. The different activation of the FA pathway may partly account for the phenotypic variation seen in FA patients. ..
  30. Pace P, Johnson M, Tan W, Mosedale G, Sng C, Hoatlin M, et al. FANCE: the link between Fanconi anaemia complex assembly and activity. EMBO J. 2002;21:3414-23 pubmed
    ..Disease-associated FANCC mutants do not bind to FANCE, cannot accumulate in the nucleus and are unable to prevent chromosome breakage. ..
  31. Siddique M, Nakanishi K, Taniguchi T, Grompe M, D Andrea A. Function of the Fanconi anemia pathway in Fanconi anemia complementation group F and D1 cells. Exp Hematol. 2001;29:1448-55 pubmed
    ..The recently cloned FANCF protein is required for FANCD2 activation, and the yet uncloned FANCD1 protein functions further downstream or independently of the FA pathway. ..
  32. Xie Y, de Winter J, Waisfisz Q, Nieuwint A, Scheper R, Arwert F, et al. Aberrant Fanconi anaemia protein profiles in acute myeloid leukaemia cells. Br J Haematol. 2000;111:1057-64 pubmed
    ..Our results suggest that a significant proportion of general AML is characterized by a disturbance of the 'FA pathway' that may represent an early event in the development of this type of leukaemia. ..