Disease relevance of ALX4

• In addition, ALX4 methylation was frequently observed in adenocarcinomas of the esophagus (12/14), stomach (11/15), and bile ducts (4/5) compared with all other cancers (P < .001) [1].
• Conclusions: Apart from colon adenomas and primary and metastatic colorectal cancers, ALX4 is frequently methylated in adenocarcinomas of the gastrointestinal tract [1].
• ALX4 methylation was also analyzed in the serum of 30 patients with colon cancer [1].
• Methylation of ALX4 was analyzed in colorectal adenomas and cancers, in the liver metastases of patients with colorectal cancer, and in 61 other neoplasias, including gastric, esophageal, and hepatocellular cancer and cholangiocarcinoma [1].
• ALX4 gene methylation in sera of patients with cancer may thus serve as a methylation-specific test for colon and other gastrointestinal cancers [1].

High impact information on ALX4

• Haploinsufficiency of the human homeobox gene ALX4 causes skull ossification defects [2].
• We previously identified mutations of MSX2 in non-syndromic PFM and demonstrated genetic heterogeneity [2].
• Methods: Using methylation-specific arbitrarily primed polymerase chain reaction, a fragment of the Aristaless-like homeobox-4 (ALX4) gene that was highly methylated in colon adenomas and cancer was identified [1].
• During murine embryogenesis, expression of the paired-like homeodomain protein Alx4 is restricted to tissues whose development depends on the expression of lymphoid enhancer factor-1 (LEF-1) [3].
• In plants, farnesyl diphosphate (FPP) and geranylgeranyl diphosphate (GGPP) are precursors to many isoprenoids having essential functions [4].

Chemical compound and disease context of ALX4

• We previously reported the isolation of a partial-length human fetal-liver cDNA encoding farnesyl diphosphate (FPP) synthase (EC 2.5.1.10) and the expression of an active FPP synthase fusion protein in Escherichia coli [5].
• Recombinant MxpSS1 produced in Escherichia coli, after removal of an N-terminal thioredoxin fusion, had a K(m) for FPP of 1.91+/-0.1 muM and k(cat) of 0.18 s(-1), and converted farnesyl diphosphate (FPP) into four products, the major two being cis-muurola-3,5-diene (45%) and cis-muurola-4(14),5-diene (43%) [6].

Biological context of ALX4

• The ALX4 homeobox gene is mutated in patients with ossification defects of the skull (foramina parietalia permagna, OMIM 168500) [7].
• Starting from a BAC/P1/cosmid contig of the DEFECT 11 region on chromosome 11, we have now isolated the ALX4 gene, a previously unidentified member of the ALX homeobox gene family in humans [7].
• Mutation analysis of the ALX4 gene in three unrelated FPP families without the MSX2 mutation identified mutations in two families, indicating that mutations in ALX4 could be responsible for these skull defects and suggesting further genetic heterogeneity of FPP [7].
• To evaluate the reliability of the measurements of left and right ventricular functions with QBS, we performed QBS, as well as first-pass pool (FPP) and ECG-gated blood-pool (GBP) studies on planar images in 41 patients and 8 healthy volunteers [8].
• The biogenesis of these JHs requires the synthesis of ethyl-substituted farnesyl diphosphate (FPP) by FPP synthase (FPPS) [9].

Anatomical context of ALX4

• Lipoxin A4 (LXA4) is a potent eicosanoid that inhibits IL-1beta-induced activation of human fibroblast like synoviocytes (FLS) via the ALX4 receptor [10].
• In situ hybridization showed that Alx4 and Msx2 are expressed in the cranial skeletogenic mesenchyme and in the growing calvarial bones [11].

Associations of ALX4 with chemical compounds

• The corresponding synthases (FPP synthase [FPPS] and GGPP synthase [GGPPS]) catalyze, respectively, the addition of two and three isopentenyl diphosphate molecules to dimethylallyl diphosphate [4].
• Identification of peroxisomal targeting signals in cholesterol biosynthetic enzymes. AA-CoA thiolase, hmg-coa synthase, MPPD, and FPP synthase [12].
• Their activity is compared to that of the previously described catalyst 2-formyl-4-pyrrolidinopyridine (FPP), which contains an aldehyde at the 2-position of the pyridine [13].
• The catalysts which contain ketones at the 2-position range in reactivity from 10 times slower to slightly faster than FPP, and certain of these are much more selective for the methanolysis of hydroxy esters than FPP [13].
• Reintroduction of the serine at position 531 into MxpSS2 by site-directed mutagenesis restored EbetaF synthase activity (K(m) for FPP 0.98+/-0.12 muM, k(cat) 0.1 s(-1)), demonstrating the crucial role of this residue in the enzyme activity [6].

Other interactions of ALX4

• Similarly, the presence of biparietal foramina has been shown to be associated with the deletion of ALX4 located proximally to EXT2 [14].

Analytical, diagnostic and therapeutic context of ALX4

• Further sequence analysis demonstrated that the human orthologue (ALX4) of the mouse Aristaless-like 4 gene (Alx4) is contained within this 11p clone [15].
• ALX4 expression was detected by reverse transcriptase polymerase chain reaction in bovine fetal limb bones [16].
• Changes in functional anatomy were quantified using transperineal ultrasonography to measure the bladder neck position at rest, maximum PFM contraction and maximum Valsalva manoeuvre [17].
• Bladder neck mobility on perineal ultrasonography was assessed immediately before and on completing a 14-week programme of 'PFM rehabilitation'. Treatment outcome was assessed using a standardized pad-test and a condition-specific, validated quality-of-life questionnaire (King's Health Questionnaire) [17].
• Rationale for the utilization of bonded nonmetal onlays as an alternative to PFM crowns [18].

References