Disease relevance of FOXK2

• Chromosomal mapping localizes the ILF gene to human chromosome 17q25, which is a site of chromosomal translocations in some cases of human acute myelogous leukemias [1].
• Recently we isolated a cellular DNA binding protein, designated interleukin enhancer binding factor (ILF), that binds to purine-rich regulatory motifs in both the HIV-1 LTR and the IL2 promoter [1].
• A comparison with the genes comprising the signature of other small B-cell lymphomas identified 3 genes whose expression distinguishes SMZL, namely ILF1, SENATAXIN, and CD40 [2].
• Randomised phase II evaluation of irinotecan plus high-dose 5-fluorouracil and leucovorin (ILF) vs 5-fluorouracil, leucovorin, and etoposide (ELF) in untreated metastatic gastric cancer [3].
• Both regimens were well tolerated, the main grade 3/4 toxicities being diarrhoea (18%, ILF) and neutropenia (57%, ELF) [3].

High impact information on FOXK2

• ILF can bind to purine-rich regulatory motifs such as the human T-cell leukemia virus-long terminal region and the interleukin-2 promoter [4].
• Interleukin enhancer binding factor (ILF) is a human transcription factor and a new member of the winged helix/forkhead family [4].
• In the current study, we demonstrated that the winged-helix transcription factor IL-2 enhancer binding factor (ILF) is constitutively expressed in both resting and activated Jurkat cells and binds to two adjacent sequence motifs immediately downstream of the binding site for NFAT [5].
• One of these elements has a high degree of homology with consensus binding sites for a variety of winged-helix DNA binding proteins, and the second site functions to modulate ILF binding [5].
• Mutagenesis of each of the two sequence elements required for ILF binding decreased IL-2 promoter activity when assayed in transfection assays [5].

Chemical compound and disease context of FOXK2

• An open-label randomised comparison of efficacy and tolerability of irinotecan plus high-dose 5-fluorouracil (5-FU) and leucovorin (LV) (ILF) with etoposide plus 5-FU/LV (ELF) in patients with untreated metastatic or locally advanced gastric cancer [3].
• Weekly treatment with irinotecan, folinic acid and infusional 5-fluorouracil (ILF) in patients with advanced gastric cancer [6].

Biological context of FOXK2

• These results suggest that important regulatory sequences in the IL-2 promoter are bound by ILF and that this binding may be involved in the control of IL-2 gene expression [5].
• Characterization and chromosomal mapping of the gene encoding the cellular DNA binding protein ILF [1].

Anatomical context of FOXK2

• Good demarcation of the CCB with ILF and poor demarcation of the deep border of the hyaline band, because of overlapping inflammatory cells, were the apparent causes [7].

Associations of FOXK2 with chemical compounds

• One cycle of ILF comprised six once-weekly infusions of irinotecan 80 mg m(-2), LV 500 mg m(-2), 24-h 5-FU 2000 mg m(-2), and ELF comprised three once-daily doses of etoposide 120 mg m(-2), LV 300 mg m(-2), 5-FU 500 mg m(-2) [3].

Other interactions of FOXK2

• Forkhead associated (FHA) domain and FOX domain were conserved among human FOXK1, FOXK2, mouse FoxK1, and Xenopus Foxk2 [8].
• Although ILF bound constitutively to the IL-2 promoter, it was not detected as a component of the NFAT complex [5].

Analytical, diagnostic and therapeutic context of FOXK2

• For ILF and ELF, respectively, median progression-free survival was 4.5 vs 2.3 months, time to treatment failure was 3.6 vs 2.2 months (P = 0.4542), and overall survival was 10.8 vs 8.3 months (P = 0.2818) [3].

References