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The Biochemical Journal Feb 1995
Review
Topics: Amino Acid Sequence; Animals; Base Sequence; Enzyme Stability; Molecular Sequence Data; Ornithine Decarboxylase; Ornithine Decarboxylase Inhibitors; Proteins
PubMed: 7864793
DOI: 10.1042/bj3060001 -
Poultry Science Jan 2011The ornithine decarboxylase (ODC) gene is a candidate gene for growth and carcass traits. It is located on chicken chromosome 3 in a region where QTL for growth and...
The ornithine decarboxylase (ODC) gene is a candidate gene for growth and carcass traits. It is located on chicken chromosome 3 in a region where QTL for growth and carcass traits have previously been detected in the F₂ population. The objectives of this study were to identify polymorphisms of the ODC gene in an F₂ resource population and to examine the effects of these ODC polymorphisms on growth and carcass traits. The F₂ resource population was obtained by crossing a Shamo male and White Plymouth Rock females. The F₂ population was then measured for growth and carcass traits and used for positional candidate gene analysis. A total of 6 novel SNP and a novel indel mutation were identified in the parental population. Three SNP (g.-638A>G, g.-465C>T, and g.-353C>T) and a 4-bp indel mutation (g.-633_-632ins) in the promoter region of the ODC gene were identified in the parental population, and 2 haplotypes composed of these mutations were segregated in the parental population. A QTL analysis was performed, and the QTL for some growth and carcass traits were detected at a significant level and on a similar position to the ODC gene. Significant associations were found between haplotypes in the promoter region of the ODC gene and these traits in the F₂ population, and the effect of haplotype on BW at 9 wk of age was the most significant. The haplotypes of the ODC gene found in this study might help in understanding the genetic structure of growth and carcass traits and in improving these traits directly by MAS. Therefore, further functional studies are necessary to evaluate the effects of promoter mutations at a molecular level.
Topics: Animals; Body Composition; Breeding; Chickens; Crosses, Genetic; Female; Genotype; Least-Squares Analysis; Male; Ornithine Decarboxylase; Polymorphism, Genetic; Quantitative Trait Loci
PubMed: 21177441
DOI: 10.3382/ps.2010-01119 -
The Journal of Biological Chemistry Oct 2006Ornithine decarboxylase (ODC), a key enzyme in the biosynthesis of polyamines, is a labile protein that is regulated by interacting with antizymes (AZs), a family of...
Ornithine decarboxylase (ODC), a key enzyme in the biosynthesis of polyamines, is a labile protein that is regulated by interacting with antizymes (AZs), a family of polyamine-induced proteins. Recently, a novel human gene highly homologous to ODC, termed ODC-like or ODC-paralogue (ODCp), was cloned, but the studies aimed to determine its function rendered contradictory results. We have cloned the mouse orthologue of human ODCp and studied its expression and possible function. mRNA of mouse Odcp was found in the brain and testes, showing a conserved expression pattern with regard to the human gene. Transfection of mouse Odcp in HEK 293T cells elicited an increase in ODC activity, but no signs of arginine decarboxylase activity were evident. On the other hand, whereas the ODCp protein was mainly localized in the mitochondrial/membrane fraction, ODC activity was found in the cytosolic fraction and was markedly decreased by small interfering RNA against human ODC. Co-transfection experiments with combinations of Odc, Az1, Az2, Az3, antizyme inhibitor (Azi), and Odcp genes showed that ODCp mimics the action of AZI, rescuing ODC from the effects of AZs and prevented ODC degradation by the proteasome. A direct interaction between ODCp and AZs was detected by immunoprecipitation experiments. We conclude that mouse ODCp has no intrinsic decarboxylase activity, but it acts as a novel antizyme inhibitory protein (AZI2).
Topics: Amino Acid Sequence; Animals; Carboxy-Lyases; Cell Line; Cytosol; Gene Expression Regulation; Humans; Mice; Molecular Sequence Data; Ornithine Decarboxylase; Polyamines; Proteins; Sequence Homology, Amino Acid; Tissue Distribution
PubMed: 16916800
DOI: 10.1074/jbc.M602840200 -
The Journal of Biological Chemistry Jul 1983Variant S49 mouse lymphoma cells with increased ornithine decarboxylase activity were obtained by selecting for resistance to alpha-difluoromethylornithine (DFMO), a...
Variant S49 mouse lymphoma cells with increased ornithine decarboxylase activity were obtained by selecting for resistance to alpha-difluoromethylornithine (DFMO), a specific inhibitor of the enzyme. Ornithine decarboxylase was identified as a specifically immunoprecipitable polypeptide that was made at an increased rate in the variant cells. Ornithine decarboxylase was also identified on a two-dimensional gel as a metabolically labeled polypeptide of Mr approximately 55,000 which was synthesized at an increased rate in two independently selected variants. Synthesis of this polypeptide was further augmented by treatment of cells with inhibitors of ornithine decarboxylase activity. The charge of the polypeptide was altered by treatment of either cells or cellular extracts with DFMO, a suicide substrate which binds covalently to the enzyme. This charge alteration and the inactivation of ornithine decarboxylase showed the same dependence on DFMO concentration and both effects were prevented by addition of either ornithine or putrescine. Pulse-chase experiments showed that the half-life of the ornithine decarboxylase polypeptide in these variant cells was 45 min. We conclude that ornithine decarboxylase is made at an increased rate in the resistant variants and that the polypeptide turns over rapidly.
Topics: Animals; Carboxy-Lyases; Cell Line; Drug Resistance; Eflornithine; Electrophoresis, Polyacrylamide Gel; Kinetics; Lymphoma; Mice; Neoplasms, Experimental; Ornithine; Ornithine Decarboxylase; Ornithine Decarboxylase Inhibitors
PubMed: 6408089
DOI: No ID Found -
Biochemical and Biophysical Research... Nov 2018Non-melanoma skin cancer (NMSC) is the most commonly diagnosed cancer in the United States. Ultraviolet-B (UVB) irradiation is the primary carcinogen responsible for...
Non-melanoma skin cancer (NMSC) is the most commonly diagnosed cancer in the United States. Ultraviolet-B (UVB) irradiation is the primary carcinogen responsible for stimulating NMSC development. Ornithine Decarboxylase (ODC), the first rate-limiting enzyme in the synthesis of polyamines, is upregulated in response to a variety of proliferation stimuli, including UVB exposure. Our previous studies have demonstrated regulation of ODC synthesis by the mammalian target of rapamycin complex 1 (mTORC1) in cells transformed by oncogenic Ras. The goal of these studies was to better understand the link between mTORC1 and ODC in nontransformed cells treated with UVB. We show that the ablation of mTORC1 activity by conditional knockout of its essential component Raptor led to decreased levels of ODC protein both before and after exposure to 10 mJ/cm UVB. Moreover, ODC mRNA was destabilized in the absence of Raptor, suggesting post-transcriptional regulation. We have previously shown that the ODC transcript is stabilized by the RNA binding protein (RBP) human antigen R (HuR), and the intracellular localization of HuR responds to changes in mTORC1 activity. To expand these studies, we investigated whether HuR functions to regulate ODC mRNA stability after UVB exposure. Our results show an increased localization of HuR to the cytoplasm after UVB exposure in wild-type cells compared to Raptor knockout cells, and this is accompanied by greater association of HuR with the ODC transcript. These data suggest that the localization of HuR in response to UVB is influenced, at least in part, by mTORC1 and that HuR can bind to and stabilize ODC mRNA after UVB exposure in an mTORC1-dependent manner.
Topics: Animals; Binding Sites; Cells, Cultured; Fibroblasts; Humans; Mechanistic Target of Rapamycin Complex 1; Mice; Ornithine Decarboxylase; RNA, Messenger; Receptors, Antigen; Transcription, Genetic; Ultraviolet Rays
PubMed: 30314695
DOI: 10.1016/j.bbrc.2018.10.019 -
The Biochemical Journal Dec 2000The polyamines putrescine, spermidine and spermine play an essential role in cell differentiation and proliferation. Inhibition of the rate-limiting enzymes of polyamine...
The ornithine decarboxylase domain of the bifunctional ornithine decarboxylase/S-adenosylmethionine decarboxylase of Plasmodium falciparum: recombinant expression and catalytic properties of two different constructs.
The polyamines putrescine, spermidine and spermine play an essential role in cell differentiation and proliferation. Inhibition of the rate-limiting enzymes of polyamine biosynthesis, ornithine decarboxylase (ODC) and S-adenosylmethionine decarboxylase (AdoMetDC), has been proposed as a therapeutic strategy against cancer and parasitic infections. In the case of Plasmodium falciparum, the causative agent of malaria tropica, this approach is especially interesting, because here both key enzymes, ODC and AdoMetDC, are combined in a bifunctional protein, ODC/AdoMetDC. This arrangement has not been found in any other organism investigated so far. We report the cloning and recombinant expression of the ODC domain of P. falciparum in Escherichia coli. First, we expressed the mere recombinant ODC domain (rPfODC). Secondly, we expressed the recombinant ODC domain in conjunction with the preceding part of the hinge region of the bifunctional ODC/AdoMetDC (rPfHinge-ODC). K(m) values for L-ornithine were 47.3 microM for the rPfHinge-ODC and 161. 5 microM for the rPfODC. Both recombinant enzymes were inhibited by putrescine, but the K(i) value for the rPfHinge-ODC was 50.4 microM (IC(50)=157 microM), whereas the IC(50) for the rPfODC was 500 microM. Spermidine was a weak inhibitor in both cases. alpha-Difluoromethylornithine inhibited the rPfHinge-ODC with a K(i) value of 87.6 microM. For two novel ODC inhibitors, CGP52622A and CGP54619A, the K(i) values of the rPfHinge-ODC were in the nanomolar range.
Topics: Adenosylmethionine Decarboxylase; Animals; Base Sequence; Catalysis; Cloning, Molecular; DNA Primers; Electrophoresis, Polyacrylamide Gel; Ornithine Decarboxylase; Ornithine Decarboxylase Inhibitors; Plasmodium falciparum; Recombinant Proteins
PubMed: 11085920
DOI: No ID Found -
Nature Microbiology Apr 2020Polyamines are essential metabolites that play an important role in cell growth, stress adaptation and microbial virulence. To survive and multiply within a human host,...
Polyamines are essential metabolites that play an important role in cell growth, stress adaptation and microbial virulence. To survive and multiply within a human host, pathogenic bacteria adjust the expression and activity of polyamine biosynthetic enzymes in response to different environmental stresses and metabolic cues. Here, we show that ornithine capture by the ribosome and the nascent peptide SpeFL controls polyamine synthesis in γ-proteobacteria by inducing the expression of the ornithine decarboxylase SpeF, via a mechanism involving ribosome stalling and transcription antitermination. In addition, we present the cryogenic electron microscopy structure of an Escherichia coli ribosome stalled during translation of speFL in the presence of ornithine. The structure shows how the ribosome and the SpeFL sensor domain form a highly selective binding pocket that accommodates a single ornithine molecule but excludes near-cognate ligands. Ornithine pre-associates with the ribosome and is then held in place by the sensor domain, leading to the compaction of the SpeFL effector domain and blocking the action of release factor 1. Thus, our study not only reveals basic strategies by which nascent peptides assist the ribosome in detecting a specific metabolite, but also provides a framework for assessing how ornithine promotes virulence in several human pathogens.
Topics: Amino Acid Sequence; Bacterial Proteins; Base Sequence; Binding Sites; Enterococcus faecalis; Escherichia coli; Models, Molecular; Ornithine; Ornithine Decarboxylase; Peptide Termination Factors; Phylogeny; Polyamines; Protein Binding; Protein Biosynthesis; Protein Interaction Domains and Motifs; RNA, Transfer; Ribosomes; Salmonella typhimurium; Sequence Alignment; Sequence Homology, Amino Acid; Thermus thermophilus; Virulence
PubMed: 32094585
DOI: 10.1038/s41564-020-0669-1 -
Cancer Prevention Research... Jan 2010Bailey et al. report in this issue of the journal (beginning on page 35) one of the first successful trials of basal cell carcinoma (BCC) prevention. Oral... (Review)
Review
Bailey et al. report in this issue of the journal (beginning on page 35) one of the first successful trials of basal cell carcinoma (BCC) prevention. Oral alpha-difluoromethyl-dl-ornithine (DFMO) reduced new BCCs in patients with a prior history of nonmelanoma skin cancer. DFMO is an inhibitor of ornithine decarboxylase, a key enzyme in the polyamine biosynthetic pathway. This perspective on Bailey et al. discusses our knowledge of the contribution of polyamines to BCC pathogenesis, how this knowledge advanced the development of a new method to prevent BCCs, and prospects for future studies of DFMO in BCC prevention.
Topics: Animals; Carcinoma, Basal Cell; Humans; Ornithine Decarboxylase; Skin Neoplasms
PubMed: 20051367
DOI: 10.1158/1940-6207.CAPR-09-0248 -
BioMed Research International 2014Malaria is a deadly infectious disease which affects millions of people each year in tropical regions. There is no effective vaccine available and the treatment is based... (Review)
Review
Malaria is a deadly infectious disease which affects millions of people each year in tropical regions. There is no effective vaccine available and the treatment is based on drugs which are currently facing an emergence of drug resistance and in this sense the search for new drug targets is indispensable. It is well established that vitamin biosynthetic pathways, such as the vitamin B6 de novo synthesis present in Plasmodium, are excellent drug targets. The active form of vitamin B6, pyridoxal 5-phosphate, is, besides its antioxidative properties, a cofactor for a variety of essential enzymes present in the malaria parasite which includes the ornithine decarboxylase (ODC, synthesis of polyamines), the aspartate aminotransferase (AspAT, involved in the protein biosynthesis), and the serine hydroxymethyltransferase (SHMT, a key enzyme within the folate metabolism).
Topics: Animals; Antioxidants; Aspartate Aminotransferases; Glycine Hydroxymethyltransferase; Humans; Malaria; Ornithine Decarboxylase; Plasmodium falciparum; Vitamin B 6
PubMed: 24524072
DOI: 10.1155/2014/108516 -
Asian Pacific Journal of Cancer... 2012Ornithine decarboxylase (ODC), the first enzyme in the polyamine biosynthesis, plays an important role in tumor progression, cell proliferation and differentiation. In...
Ornithine decarboxylase (ODC), the first enzyme in the polyamine biosynthesis, plays an important role in tumor progression, cell proliferation and differentiation. In recent years, ODC has been the subject of intense study among researchers, as a target for anti-cancer therapy and specific inhibitory agents, have the potential to suppress carcinogenesis and find applications in clinical therapy. In particular, it is suggested that ODC is a promising candidate target for natural products in cancer chemoprevention. Future exploration of ornithine decarboxylase inhibitors present in nature may offer great hope for finding new cancer chemopreventive agents.
Topics: Antineoplastic Agents; Biological Products; Enzyme Inhibitors; Humans; Neoplasms; Ornithine Decarboxylase; Ornithine Decarboxylase Inhibitors
PubMed: 22901233
DOI: 10.7314/apjcp.2012.13.5.2425