Disease relevance of FANCF

• Inactivation of the Fanconi Anemia (FANC-BRCA) pathway via promoter methylation of the FANCF gene has been proposed to be responsible for variation in cisplatinum (CDDP) sensitivity seen in ovarian and HNSCCs [1].
• FANCF-deregulated CC cell lines also exhibit a chromosomal hypersensitivity phenotype after exposure to an alkylating agent, a characteristic of FA patients [2].
• Inactivation of the FANC-BRCA pathway via promoter methylation of the FANCF gene renders cells sensitive to DNA crosslinking agents, and has been identified in ovarian cancer cell lines and sporadic primary tumor tissues [3].
• In adenocarcinomas of the lung, FANCF promoter methylation was a significant predictor of poor survival with a hazard ratio of 3.1 (95% CI 1.2-7.9) [3].
• A 68.5-kd chimeric protein (His-M195FANCF) was expressed, consisting of a His tag, a single-chain antibody to the myeloid antigen CD33, and the FANCF protein, as well as a 43-kd His-FANCF fusion protein lacking the antibody motif, in Escherichia coli [4].

Psychiatry related information on FANCF

• FANCF methylation was associated with a shorter duration of tobacco use (P=0.03) and a younger age of starting smoking (P=0.06) in NSCLC, and with a greater number of years of alcohol drinking (P=0.02) in HNSCC [3].
• In contradistinction, study of the personality and the emotional changes (MMPI and FAF) failed to demonstrate pathological scores in the 3 groups with different CT lesions, without any significant difference being found between the groups with temporal lesions and those with other focal brain lesions or diffuse brain damage [5].

High impact information on FANCF

• Mono-ubiquitination of FANCD2, a measure of the function of this pathway, and cisplatin resistance were restored by functional complementation with FANCF, a gene that is upstream in this pathway [6].
• 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 [6].
• FANCF inactivation in ovarian tumors resulted from methylation of its CpG island, and acquired cisplatin resistance correlated with demethylation of FANCF [6].
• Structure of the N-terminal half of gelsolin bound to actin: roles in severing, apoptosis and FAF [7].
• 1. Forearm vascular resistance (mean arterial pressure/FAF) decreased by 72% [8].

Biological context of FANCF

• Based upon the homology between human and Xenopus laevis FANCF, we carried out an extensive mutagenesis study to examine which domains are functionally important and to gain more insight into the function of FANCF [9].
• RESULTS: FANCF protein expression is normal in cells derived from all FA complementation groups except FA-F and does not vary during cell cycle progression [10].
• While significant differences were found in CDDP cytotoxicity, Fanconi pathway defects are an infrequent cause, as no evidence of transcriptional down-regulation of FANCF or other FANC mRNAs, or functional FANC-BRCA pathway defects were observed [1].
• Here, we show that FANCF gene is disrupted by either promoter hypermethylation and/or deregulated gene expression in a majority of CC [2].
• Inhibition of DNA methylation and histone deacetylases induces FANCF gene re-expression in CC cell lines [2].

Anatomical context of FANCF

• In contrast, human fibroblasts and Schwannoma cell cultures showed only a limited capacity to cleave FAF gelsolin, although the cleavage mechanism per se seems to be similar in the various cell types [11].
• Single FAF and RAM are useful materials for one-stage reconstruction of complex three-dimensional oral and maxillofacial defects requiring replacement of skin, mucosa, and intervening soft tissues [12].
• For control group, IVM oocytes were fertilized using frozen-thawed camel spermatozoa separated by swim-up method then suspended in Fert-TALP medium supplemented with 6 mg/ml BSA (FAF) + 10 mug/ml heparin [13].

Associations of FANCF with chemical compounds

• The DNA was treated with bisulfite and then analyzed with methylation-specific PCR (MSP) to detect FANCF methylation [14].
• Combined infusions (n = 9) of maximum forearm vasodilator doses of alpha-hANP and nitroprusside increased FAF to 22.7 +/- 3.4; this additive vasodilator effect of alpha-hANP and nitroprusside is consistent with their different actions on the guanylate cyclase system [8].
• Intraindividually, the maximum dose of alpha-hANP induced an increase in FAF that was 60% of the maximum response to sodium nitroprusside (14.1 +/- 1.8) [8].
• Formyl-FAF or formyl-methanopterin (YFC, a very rapidly labelled compound during 14C pulse labeling) has been implicated as an obligate intermediate in methanogenesis, since methanopterin or FAF is an essential component of the carbon dioxide reducing factor in dialyzed extract methanogenesis [15].
• FAF also carries the carbon at the methylene and methyl oxidation levels.(ABSTRACT TRUNCATED AT 400 WORDS)[15]

Physical interactions of FANCF

• We found that the C terminus of FANCF interacts directly with FANCG and allows the assembly of other FA proteins into a stable complex [9].
• 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 [16].

Other interactions of FANCF

• The recent cloning of the FANCF and FANCE genes has allowed us to investigate the interaction of the proteins encoded by five of the seven complementation groups of FA [17].
• The interaction between FANCG and FANCF was ablated by a Leu71Pro mutant of FANCG [18].
• Our x-ray crystallographic studies of the C-terminal domain of FANCF reveal a helical repeat structure similar to the Cand1 regulator of the Cul1-Rbx1-Skp1-Fbox(Skp2) ubiquitin ligase complex [16].
• Combined bisulphite restriction analysis for methylation of FANCF, FANCB and NBS1 was used to investigate 81 sporadic acute childhood leukaemias [19].

Analytical, diagnostic and therapeutic context of FANCF

• The expression of FANCF mRNA was detected with Reverse transcription-polymerase chain reaction (RT-PCR) [14].
• Free AFP (FAFP) levels were determined in parallel in each sample by means of an automated immunoassay system [20].

References