Methional derived from 4-methylthio-2-oxobutanoate is a cellular mediator of apoptosis in BAF3 lymphoid cells

Quash, G.; Roch, Anne-Marie; Chantepie, Jacqueline; Michal, Yvonne; Fournet, Guy; Dumontet, Charles

doi:10.1042/bj3051017

Cited by 26 publications

(32 citation statements)

References 44 publications

(59 reference statements)

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“…First, the adduct appears within 8 h of treatment with CD437, at a point coincident with the onset of apoptosis; 11 secondly, non-apoptotic retinoids RA and CD666 do not cause formation of this adduct, and finally, all CITs are DNA damage-response genes and ei24 is a critical mediator of apoptosis. Although alternative mechanisms cannot be completely ruled out, 40 we believe that our data can be most readily explained by this interpretation. The DNA damage-sensing mechanism in S91 cells then triggers induction of CITs which has dramatic effects on cell physiology.…”

Section: Discussionmentioning

confidence: 78%

Retinoic acid receptor-independent mechanism of apoptosis of melanoma cells by the retinoid CD437 (AHPN)

et al. 2001

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Retinoic acid (RA) induces differentiation of S91 melanoma cells through activation of RA receptor (RAR)g without affecting cell viability. The novel RARg-agonist CD437 (AHPN), however, also induces concomitant apoptosis through an unknown mechanism which was investigated here. By utilizing DNA microarray analysis, five apoptosis-associated, CD437-induced transcripts (CITs) were identified. Interestingly, all CITs are also regulated by p53 in a DNA damage response, and consistent with this interpretation, CD437 was found to cause DNA adduct-formation. However, p53 is not required for CD437-dependent regulation of CITs. Among this set of genes, induction of p21 WAF1/CIP1 is likely to be responsible for early S-phase growth-arrest of CD437-treated cells, whereas ei24 is a critical mediator of CD437-induced apoptosis in S91 cells. These data suggest an RARindependent mechanism in which CD437 causes DNA adduct-formation, resulting in induction of a p53-independent DNA damage response, and subsequent growth-arrest and apoptosis. CD437-mediated DNA adduct-formation may also explain its apoptotic effects in other cell types. Cell Death and Differentiation (2001) 8, 878 ± 886.

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Section: Discussionmentioning

confidence: 78%

Retinoic acid receptor-independent mechanism of apoptosis of melanoma cells by the retinoid CD437 (AHPN)

et al. 2001

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“…Our studies cannot determine whether MTOB is a direct regulator of ODC or whether some metabolite of MTOB is involved. Studies using BAF 3 murine lymphoid cells have demonstrated that MTOB can be converted to malondialdehyde and methional in cell extracts (45). Interestingly, MTOB and methional at high concentrations can induce apoptosis in BAF 3 cells.…”

Section: Discussionmentioning

confidence: 99%

Methylthioadenosine Phosphorylase Regulates Ornithine Decarboxylase by Production of Downstream Metabolites

Subhi¹,

Diegelman

Porter

et al. 2003

Journal of Biological Chemistry

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A quarter century ago, Toohey (10) first recognized that certain murine malignant hematopoietic cell lines lacked methylthioadenosine phosphorylase (MTAP) 1 activity. MTAP is a key enzyme in the methionine salvage pathway (see Fig. 1). This pathway functions to salvage methylthioadenosine (MTA), which is formed as a by-product of polyamine metabolism. Phosphorolysis of MTA by MTAP results in the conversion of MTA into adenine and methylthioribose 1-phosphate. A series of reactions then salvages the methyl-thio group from methylthioribose 1-phosphate to form methionine. This pathway has been most extensively studied in Klebsiella pneumoniae (11-14) but has also been shown to exist in rat liver (15-17) and in Saccharomyces cerevisiae (18,19).Loss of MTAP activity through gene deletion is common in many kinds of human cancers including non-small cell lung cancer, glioma, T-cell acute leukemia, bladder cancer, osteosarcoma, and endometrial cancer (2-5, 20 -22). Recently, we found that expression of MTAP in an MTAP-deleted breast adenocarcinoma cell line (MCF-7) resulted in a dramatic inhibition of tumorigenicity in vitro and in vivo, showing that MTAP can function as a tumor suppressor gene (1). We also found that MTAP expression causes a significant decrease in intracellular polyamine levels and alters the ratio of putrescine to total polyamines. Consistent with this observation, the polyamine biosynthesis inhibitor ␣-difluoromethylornithine inhibits the ability of MTAP-deficient MCF-7 cells to form colonies in soft agar, whereas the addition of the polyamine putrescine stimulates colony formation in MTAP-expressing MCF-7 cells. These results indicate that the tumor suppressor activity of MTAP may be mediated by its effect on the intracellular polyamine pools.Polyamines are small, aliphatic amines involved in a variety of cellular processes including transcription and apoptosis (8). The rate-limiting enzyme in the production of polyamines is ornithine decarboxylase (ODC). Elevated ODC activity has been observed in a wide variety of human and animal tumors, and overexpression of ODC in NIH/3T3 cells is sufficient to cause transformation in vitro (7,23). Transgenic mice overexpressing ODC in skin develop skin tumors at a high frequency (9, 24). These observations show that overexpression of ODC is tumorigenic.Examination of the S. cerevisiae genome for MTAP homologues suggests that the MEU1 gene, with 35% identity and 53% similarity over 275 amino acids, may encode the yeast MTAP homologue. Furthermore, recent studies show that cells lacking MEU1, in combination with a mutation that allows yeast to take up methylthioadenosine, are unable to grow on medium containing MTA as the sole sulfur source (25). MEU1 was initially identified in a screen for genes that regulate expression of the yeast ADH2 gene (26). Overexpression of MEU1 increased ADH2 expression, whereas deletion of MEU1 resulted in reduced ADH2 expression. At the time these experiments were published, the MTAP gene had not yet been identified, so the relatio...

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“…[11]. MTOB является непосредственным предшествен-ником метионина в реутилизационном пути и может превращаться в метионал -индуктор апоптоза [12]. Совместно с метилтрансферазой SAM участвует в ре-акции образования карнитина из ГАМК [11].…”

Section: клиническая онкогематологияunclassified

Pathological Metabolism of Methionine in Malignant Cells Is a Potential Target for the Antitumor Therapy

VS¹,

Davydov²,

Anufrieva³

et al. 2017

Клиническая онкогематология

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This review presents the characteristics of the cellular metabolism of methionine, as well as known data on the mechanisms of the development of methionine dependence in malignant cells. The possibilities of using a non-methionine diet for the control of the tumor growth in patients with various forms of cancer are considered. The information about methionine Y-lyase, an enzyme providing elimination of methionine from plasma, is provided. Its role as a potential antitumor enzyme is disclosed. Data on cytotoxic activity of the enzyme, obtained from various sources, and information on tumor models and cell cultures, showing methionine dependence are summarised.

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Methional derived from 4-methylthio-2-oxobutanoate is a cellular mediator of apoptosis in BAF3 lymphoid cells

Cited by 26 publications

References 44 publications

Retinoic acid receptor-independent mechanism of apoptosis of melanoma cells by the retinoid CD437 (AHPN)

Retinoic acid receptor-independent mechanism of apoptosis of melanoma cells by the retinoid CD437 (AHPN)

Methylthioadenosine Phosphorylase Regulates Ornithine Decarboxylase by Production of Downstream Metabolites

Pathological Metabolism of Methionine in Malignant Cells Is a Potential Target for the Antitumor Therapy

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