Disease relevance of HC-Toxin

• We examined the regulation of 15-LO-1 in human tissue and the colorectal carcinoma cell lines Caco-2 and SW-480 by treatment with histone deacetylase (HDAC) inhibitors: NaBT, trichostatin A (TSA) and HC toxin [1].
• Antiproliferative effect of trichostatin A and HC-toxin in T47D human breast cancer cells [2].

High impact information on HC-Toxin

• A gene, HDC1, related to the Saccharomyces cerevisiae histone deacetylase (HDAC) gene HOS2, was isolated from the filamentous fungus Cochliobolus carbonum, a pathogen of maize that makes the HDAC inhibitor HC-toxin [3].
• An ortholog of SNF1, ccSNF1, was isolated from the maize pathogen Cochliobolus carbonum, and ccsnf1 mutants of HC toxin-producing (Tox2(+)) and HC toxin-nonproducing (Tox2(-)) strains were created by targeted gene replacement [4].
• Race 1 isolates of the filamentous fungus Cochliobolus carbonum are exceptionally virulent on certain genotypes of maize due to production of a cyclic tetrapeptide, HC-toxin [5].
• Two other genes known or thought to be important for HC-toxin biosynthesis, TOXA and TOXC, are also on the same chromosome in multiple copies [5].
• HDs from chicken and the myxomycete Physarum polycephalum were also inhibited, indicating that the host selectivity of HC toxin is not determined by its inhibitory effect on HD [6].

Biological context of HC-Toxin

• In vivo treatment of embryos with HC toxin caused the accumulation of highly acetylated histone H4 subspecies and elevated acetate incorporation into H4 in susceptible-genotype embryos but not in the resistant genotype [6].
• Consistent with these results, we propose a model in which HC toxin promotes the establishment of pathogenic compatibility between C. carbonum and maize by interfering with reversible histone acetylation, which is implicated in the control of fundamental cellular processes, such as chromatin structure, cell cycle progression, and gene expression [6].
• TOXE plays a specific regulatory role in HC-toxin production and, therefore, pathogenicity by C. carbonum [7].
• Disruption of both copies at either site resulted in loss of ability to produce HC-toxin and loss of host-selective pathogenicity, but the mutants displayed different biochemical phenotypes depending on the site of disruption [8].
• The cyclic peptide synthetase catalyzing HC-toxin production in the filamentous fungus Cochliobolus carbonum is encoded by a 15.7-kilobase open reading frame [9].

Anatomical context of HC-Toxin

• We investigated the induction of the human fetal globin gene using five potent histone deacetylase (HDAC) inhibitors: FK-228, HC-Toxin, Trichostatin, MS-275, and Apicidin, using in vitro assays and cultures of primary human erythroblasts [10].

Associations of HC-Toxin with other chemical compounds

• The maize Hm1 gene encoding the NADPH-dependent HC-toxin reductase is capable of detoxifying HC-toxin of fungus Cochliobolus carbonum [11].
• A high molecular weight complex (430,000) is sensitive to HC-toxin and trichostatin A and shows immunoreactivity with an antibody against Cochliobolus HDC2, an enzyme homologous to yeast RPD3 [12].
• The antimitogenic activities of HC-toxin chloromethyl ketone (IC50 = 30-40 ng/mL) and chlamydocin chloromethyl ketone (IC50 = 3-10 ng/mL) were found to be 3-4-fold lower than those of the natural products themselves [13].
• PCR products representing CPS genes from Diheterospora chlamydosporia, which makes the HC-toxin analog chlamydocin, Cylindrocladium macrosporum, which makes the analog Cyl-2, and C. victoriae, which makes the unrelated cyclic pentapeptide victorin, were cloned and analysed [14].

Gene context of HC-Toxin

• In vivo treatment of meristematic tissue with the deacetylase inhibitor HC toxin does not affect the expression of the three maize histone deacetylases, whereas it causes downregulation of histone acetyltransferase B [15].
• In MCF-7 cells that contain high level estrogen receptor, trichostatin A and HC-toxin brought about three-times more potent cell growth inhibitory effect than estrogen receptor negative MDA-MB-468 cells [16].
• When fractionated by anion-exchange chromatography, extracts of resistant and sensitive isolates and species had two peaks of HDAC activity, one that was fully HC-toxin resistant and a second that was larger and sensitive [17].
• The DNA sequence encodes tryptic peptides derived from two HC-toxin biosynthetic enzymes, HC-toxin synthetase 1 (HTS-1) and HC-toxin synthetase 2 (HTS-2), indicating that these two enzymes exist in vivo as part of a single polypeptide [9].
• It is concluded that TOXG encodes an alanine racemase whose function is to synthesize D-Ala for incorporation into HC-toxin [18].

Analytical, diagnostic and therapeutic context of HC-Toxin

• In genetic crosses, HC-toxin production in the filamentous fungus Cochliobolus carbonum appears to be controlled by a single locus, TOX2 [19].

References