Disease relevance of FBXW4

• Decitabine (5-Aza-2'-deoxycytidine; DAC) plus daunorubicin as a first line treatment in patients with acute myeloid leukemia: preliminary observations [1].
• For screening the genes upregulated by the demethylating agent 5-aza-2'-deoxycytidine (DAC), cDNA microarray analysis (AceGene(R), containing 30,000 genes) was performed using gastric cancer cell lines (AGS, MKN74, MKN1, MKN45 and Kato3) treated with DAC [2].
• Encouraging response rates of about 50% in myelodysplasia with 5-azacytidine and 5-aza-2'-deoxycytidine (decitabine or DAC) have resulted in a number of phase III studies being initiated in this disorder [3].
• Preaxial involvement of the upper extremities was most commonly seen at the SHFM3 locus mapped to chromosome 10q24 (OMIM 600095) and consisted of proximally placed thumbs and/or triphalangeal thumbs (TPT), preaxial polydactyly and/or absence of the first ray [4].
• Half of the teeth, which received the acid application directly over the axial wall, were contaminated prior to the procedures with dental plaque collected from the patient's own teeth (group DAC) [5].

High impact information on FBXW4

• Either DAC treatment or enforced SOCS-3 expression sensitized the cells to TRAIL-mediated apoptosis [6].
• We mapped data from a large Turkish family with isolated SHFM to chromosome 10q24 and have narrowed the SHFM3 region from 9 cM to an approximately 2-cM critical interval between genetic markers D10S1147 and D10S1240 [7].
• This duplicated region contained a disrupted extra copy of the DACTYLIN gene and the entire LBX1 and beta-TRCP genes, known to be involved in limb development [8].
• Mutation analysis of the DACTYLIN gene, suspected to be responsible for SHFM3 in chromosome 10q24, was conducted in seven SHFM patients [8].
• The possible role of these genes in the SHFM3 phenotype is discussed [8].

Biological context of FBXW4

• We screened the coding region of DACTYLIN by single-strand conformation polymorphism and sequencing, and found no point mutations [8].
• Split hand foot malformation is associated with a reduced level of Dactylin gene expression [9].
• The Dactylin gene comprises nine exons distributed in more than 85 kb of genomic DNA and encoding a protein with four WD40 repeats and an F-box motif [10].
• In this communication we describe the clinical and molecular genetic findings in a family with a variable ectrodactyly linked to SHFM3 [11].
• In fact, linkage analysis using informative microsatellite markers indicated that SHFM3 was linked to D10S577 with a maximum LOD score of 1.15 at recombination fraction zero [12].

Anatomical context of FBXW4

• Studies of the mechanism of the interaction showed that the activity of topotecan versus each cell line correlated with the topo I activity in nuclear extracts However, there was no correlation between topo I levels and synergy and no reproducible increase in topo I activity following exposure to DAC [13].
• Since elastic properties of grafts tested experimentally have been correlated with patency results, the compliance of the human femoral artery was compared with grafts currently in use: human saphenous vein (HSV), knitted Dacron (DAC), glutaraldehyde-treated umbilical cord vein (DBM), bovine heterograft, and expanded polytetrafluoroethylene (PTFE) [14].
• We identified the presence, absence, and amount of calcification in the aortic valve (AVC), mitral annulus (MAC), descending aorta (DAC), and ascending aorta (AAC) [15].

Associations of FBXW4 with chemical compounds

• In both cell lines, sequential DAC/DP treatment induced expression of tissue factor pathway inhibitor-2 (TFPI-2), an inhibitor of Factor VII: tissue factor signal transduction known to diminish the malignant phenotype of cancer cells [16].
• We tested the treatment with a 72-h continuous infusion of low-dose 5-Aza-2'-deoxycytidine (DAC) in a group of 29 elderly patients with high-risk MDS [17].
• DAC was given as a 4-h intravenous infusion at the dose of 90 mg/m2 daily from days 1-5, while daunorubicin was administered at the dose of 50 mg/m2 on days 1-3 [1].
• The total flavonoid content calculated as quercetin-3- O-beta- D-glucuronide was 1% in the lyophilized herb used in this study and 0.5% in a commercial drug, meeting DAC standards [18].
• We demonstrated the utility of using the THAP/DAC MALDI matrix for peptide sequencing with DNA polymerase beta tryptic peptide mixture, as well as tryptic peptides derived from Xiphophorus maculatus brain extract proteins previously separated by two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) [19].

Other interactions of FBXW4

• It therefore appears that the Korean SHFM may be caused by mutation of SHFM3 [12].
• Here we show, using two different techniques, FISH and quantitative PCR that SHFM3 is caused by a minimal 325 kb duplication containing only two genes (BTRC and POLL) [20].
• Expression analysis of 13 candidate genes within and flanking the duplicated region shows that BTRC (present in three copies) and SUFU (present in two copies) are overexpressed in SHFM3 patients compared to controls [20].

Analytical, diagnostic and therapeutic context of FBXW4

• To refine the minimum duplicated region and to further characterize the SHFM3 locus, we screened 28 non-syndromic SHFM families for tandem genomic duplication of 10q24 by Southern blot and sequence analysis of the dactylin gene [21].
• SHFM3 has been shown by pulsed-field gel electrophoresis to be caused by an approximately 500 kb DNA rearrangement at 10q24 [20].

References