Affinage

ODC1

Ornithine decarboxylase · UniProt P11926

Length
461 aa
Mass
51.1 kDa
Annotated
2026-04-29
100 papers in source corpus 23 papers cited in narrative 23 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ODC1 encodes ornithine decarboxylase, the rate-limiting pyridoxal-5'-phosphate (PLP)-dependent enzyme that decarboxylates L-ornithine to putrescine, thereby governing polyamine biosynthesis and influencing cell proliferation, DNA methylation homeostasis, and inflammation resolution. ODC1 is subject to multilayered regulation: its transcription is activated by c-Myc/Max binding to tandem intronic E-boxes and by NF-κB (PMID:9162900, PMID:15240510), its mRNA is translated via both cap-dependent (eIF-4E-requiring) and IRES-mediated cap-independent mechanisms (PMID:9367873, PMID:20174632), and transcriptional elongation is modulated by two intrinsic attenuator sites (PMID:7537363). The protein is rapidly turned over through ubiquitin-independent proteasomal degradation requiring a C-terminal degron and the polyamine-induced cofactor antizyme, which binds ODC monomers, exposes an N-terminal unstructured degron, and targets the enzyme for destruction by the 26S proteasome; loss of antizyme or truncation of the C-terminal degron stabilizes ODC and elevates putrescine, driving tumorigenesis or, in humans, a syndromic neurodevelopmental disorder (Bachmann–Bupp syndrome) (PMID:2928784, PMID:8486633, PMID:21295581, PMID:30239107). Downstream, ODC-derived putrescine sustains MerTK-dependent anti-inflammatory signaling in macrophages, maintains LINE-1 DNA methylation in uroepithelial cells, and in astrocytes feeds the putrescine-to-GABA conversion pathway relevant to amyloid clearance (PMID:33406854, PMID:32123240, PMID:38216963).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1989 High

    Identification of the C-terminal degron established that ODC's notoriously short half-life is encoded in its last 37 residues, separating catalytic function from protein stability control.

    Evidence C-terminal truncation mutants in mammalian cells with pulse-chase immunoprecipitation

    PMID:2928784

    Open questions at the time
    • The trans-acting factor(s) recognizing the C-terminal degron were not identified
    • Whether additional degron elements exist elsewhere in ODC was unknown
  2. 1993 High

    Demonstration that antizyme is required for accelerated ODC degradation and that this process is ubiquitin-independent resolved the mechanism by which polyamines feed back to eliminate ODC protein.

    Evidence In vitro degradation reconstitution with antizyme immunodepletion; cycloheximide chase in mammalian cell extracts

    PMID:8486633

    Open questions at the time
    • How antizyme physically presents ODC to the proteasome was not defined
    • Role of ODC phosphorylation at Ser303 in degradation kinetics remained unclear
  3. 1995 High

    Discovery of two transcriptional attenuator sites in the ODC gene revealed an elongation-level regulatory checkpoint, showing that ODC output is controlled not only at initiation but also by RNA Pol II pausing.

    Evidence In vitro transcription in HeLa nuclear extract with purified RNA Pol II and elongation factor TFIIS

    PMID:7537363

    Open questions at the time
    • In vivo relevance of both attenuators was not demonstrated
    • Identity of the auxiliary factor required for Att.1 recognition was unknown
  4. 1997 High

    Showing that c-Myc/Max binds cooperatively to tandem E-boxes in ODC intron 1 established ODC as a direct Myc target and explained how Myc-driven proliferation channels through polyamine synthesis.

    Evidence Electrophoretic mobility shift assay with purified vaccinia-expressed c-Myc and Max on the native ODC genomic fragment

    PMID:9162900

    Open questions at the time
    • Functional consequence of tandem versus single E-box occupancy on ODC transcription in vivo was not measured
    • Whether Myc/Max binding is sufficient or requires co-activators was unresolved
  5. 1997 Medium

    Connecting ODC-mediated transformation to Sos-1/Raf-1 phosphorylation and eIF-4E-dependent ODC mRNA translation placed ODC downstream of Ras signaling and upstream of growth factor receptor remodeling.

    Evidence Immunoblotting in ODC- and ras-transformed NIH3T3 cells; antisense eIF-4E in ras-transformed fibroblasts

    PMID:9365242 PMID:9367873

    Open questions at the time
    • Direct versus indirect effects of ODC overexpression on Sos-1/Raf-1 were not delineated
    • The kinase responsible for c-Jun phosphorylation in ODC-transformed cells was not identified
  6. 1999 High

    Antizyme overexpression was shown to be sufficient to kill transformed cells and block tumor formation in vivo, validating the ODC–antizyme axis as a druggable node in cancer.

    Evidence Inducible antizyme expression in NIH3T3 cells; nude mouse tumorigenicity assay with polyamine measurements

    PMID:9926931

    Open questions at the time
    • Whether antizyme exerts ODC-independent anti-proliferative effects was not excluded
    • Therapeutic delivery of antizyme was not explored
  7. 2003 High

    The crystal structure of trypanosomal ODC with D-ornithine and the inhibitor G418 revealed the Schiff-base catalytic mechanism and an allosteric inhibition site involving active-site loop disordering.

    Evidence X-ray crystallography at 2.5 Å resolution of T. brucei ODC with substrate analog and inhibitor

    PMID:12672797

    Open questions at the time
    • Structure of mammalian ODC in complex with antizyme was not determined
    • The allosteric site's druggability for human ODC was not assessed
  8. 2004 High

    Establishing that antizyme itself is degraded by ubiquitin-dependent proteolysis inhibited by polyamines completed the feedback circuit: polyamines both induce antizyme synthesis and stabilize antizyme protein.

    Evidence Genetic identification of yeast Oaz1; frameshifting and proteasome-dependent degradation assays in S. cerevisiae

    PMID:15538383

    Open questions at the time
    • The E3 ligase ubiquitinating antizyme was not identified
    • Quantitative contribution of antizyme stabilization versus synthesis to polyamine homeostasis was unmeasured
  9. 2006 High

    In vivo genetic epistasis showed that antizyme delays Ras/MEK-driven skin tumorigenesis primarily by depleting putrescine and prolonging G2/M rather than inducing apoptosis, dissecting the cell-cycle mechanism downstream of ODC.

    Evidence MEK × antizyme double-transgenic mice; polyamine quantification; S-phase/mitotic index; TUNEL assay

    PMID:16400186

    Open questions at the time
    • Molecular target linking putrescine to G2/M transit was not identified
    • Whether spermidine/spermine contribute independently was not resolved
  10. 2010 High

    Demonstration that ZNF9 binds the ODC 5′UTR IRES and activates cap-independent translation provided the first trans-acting factor for IRES-mediated ODC regulation, with relevance to myotonic dystrophy type 2.

    Evidence Polyribosome fractionation; direct RNA binding; IRES-reporter assay in human myoblasts including DM2 patient cells

    PMID:20174632

    Open questions at the time
    • Whether ZNF9 is the sole IRES trans-acting factor for ODC mRNA was unknown
    • Structural basis of ZNF9–IRES interaction was not determined
  11. 2011 High

    Identifying an N-terminal unstructured degron (ODS) in yeast ODC that is activated by antizyme binding unified the C-terminal and N-terminal degron models: antizyme monomerizes ODC to expose the N-terminal unstructured initiation site for proteasomal threading.

    Evidence Domain-swap and extensive mutagenesis; fusion protein stability assays in S. cerevisiae

    PMID:21295581

    Open questions at the time
    • Whether mammalian ODC uses the same N-terminal unstructured degron was not tested
    • Structural details of antizyme-induced conformational change were lacking
  12. 2018 High

    Discovery that a heterozygous C-terminal truncating ODC1 mutation causes a human neurodevelopmental syndrome (Bachmann–Bupp syndrome) via protein stabilization and putrescine accumulation provided the first Mendelian disease link and validated the degron mechanism in human disease.

    Evidence Whole-exome sequencing; Sanger validation; RBC and fibroblast ODC protein and polyamine quantification

    PMID:30239107

    Open questions at the time
    • Genotype–phenotype correlation across different truncation mutations was not established
    • CNS-specific consequences of putrescine excess were not mechanistically defined
  13. 2019 High

    Quantifying 12–17-fold elevated ODC activity in patient fibroblasts and demonstrating normalization by DFMO established proof-of-concept for therapeutic inhibition in Bachmann–Bupp syndrome.

    Evidence 14C radioactive ODC activity assay; putrescine measurement; DFMO rescue in patient-derived fibroblasts

    PMID:31249027

    Open questions at the time
    • In vivo efficacy and safety of DFMO in patients was not demonstrated
    • Whether DFMO fully rescues neurodevelopmental phenotypes was unknown
  14. 2020 Medium

    Linking ODC1 knockdown to genome-wide LINE-1 demethylation and DNA double-strand breaks revealed a previously unrecognized role for polyamine metabolism in maintaining epigenomic integrity.

    Evidence siRNA knockdown in primary uroepithelial cells; LINE-1 methylation assay; γH2AX immunostaining

    PMID:32123240

    Open questions at the time
    • Which polyamine species (putrescine, spermidine, or spermine) mediates the methylation effect was not determined
    • Whether ODC1 loss affects methylation at loci beyond LINE-1 was not systematically assessed
  15. 2021 High

    Showing that macrophage ODC-derived putrescine sustains MerTK expression via histone methylation and thereby enables Erk1/2-dependent IL-10 production during efferocytosis connected polyamine biosynthesis to innate immune resolution of inflammation.

    Evidence Myeloid-specific ODC deletion; zymosan peritonitis; RNA-seq; nanoparticle-mediated silencing; putrescine rescue; Western blot for MerTK/Erk1/2

    PMID:33406854

    Open questions at the time
    • The specific histone methyltransferase downstream of putrescine was not identified
    • Relevance to chronic inflammatory diseases beyond peritonitis models was not tested
  16. 2024 Medium

    Astrocytic ODC1 knockdown cleared amyloid plaques and switched astrocytes to a regenerative state in an Alzheimer's model, positioning ODC1 as a bridge between the urea cycle and GABA production in neurodegeneration.

    Evidence Viral-mediated Odc1 knockdown in astrocytes of APP/PS1 mice; Aβ plaque immunostaining; transcriptomics; proBDNF Western blot

    PMID:38216963

    Open questions at the time
    • Whether plaque clearance is due to reduced putrescine, reduced GABA, or another metabolite was not resolved
    • Behavioral and cognitive rescue was not reported
    • Single mouse model without independent replication

Open questions

Synthesis pass · forward-looking unresolved questions
  • A high-resolution structure of mammalian ODC in complex with antizyme, the identity of the E3 ligase that ubiquitinates antizyme, the specific histone methyltransferases mediating putrescine's epigenomic effects, and in vivo clinical outcomes of DFMO in Bachmann–Bupp syndrome remain to be established.
  • No mammalian ODC–antizyme co-crystal structure exists
  • The E3 ligase for antizyme ubiquitination is unidentified
  • Clinical trial data for DFMO in Bachmann–Bupp syndrome are unavailable in the primary mechanism literature

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016829 lyase activity 2
Localization
GO:0005829 cytosol 2
Pathway
R-HSA-1430728 Metabolism 5 R-HSA-392499 Metabolism of proteins 4 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-1640170 Cell Cycle 1 R-HSA-168256 Immune System 1
Partners
AZIN1MAXMYCNQO1OAZ1ZNF9

Evidence

Reading pass · 23 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1989 A carboxyl-terminal domain of ODC (last 37 residues) is required for rapid intracellular degradation; truncation of these residues converts ODC from a short-lived protein (t½ ~1 h) to a stable protein retaining full activity for at least 4 hours. C-terminal truncation mutants expressed in mammalian cells; pulse-chase immunoprecipitation and gel electrophoresis Science High 2928784
1993 Antizyme (Az), induced by spermidine, binds to ODC and is essential for accelerated ODC degradation by the proteasome; this degradation is ubiquitin-independent and the rate correlates with antizyme levels in cell extracts. ODC is phosphorylated (likely at serine 303 in a PEST region), but antizyme promotes degradation of both phosphorylated and dephosphorylated ODC. In vitro ODC degradation system using cell extracts; immunodepletion of antizyme with anti-antizyme antibody; cycloheximide/actinomycin D experiments; pulse-chase The Journal of Biological Chemistry High 8486633
2004 In yeast, ODC antizyme (Oaz1) is itself subject to ubiquitin-mediated proteasomal degradation, and this degradation is inhibited by polyamines. Polyamines thus inhibit ODC biosynthesis by two mechanisms: inducing Oaz1 synthesis (via frameshifting) and inhibiting Oaz1 degradation. Degradation of yeast ODC by the proteasome is Oaz1-dependent. Genetic identification and characterization of yeast Oaz1; frameshifting assays; proteasome-dependent degradation assays in S. cerevisiae The EMBO Journal High 15538383
2005 ODC undergoes ubiquitin-independent degradation by the 20S proteasome regulated by NAD(P)H quinone oxidoreductase 1 (NQO1), in addition to the antizyme-mediated ubiquitin-independent 26S proteasome pathway. The regulator antizyme (Az) is itself degraded in a ubiquitin-dependent manner, as is antizyme inhibitor (AzI). Review synthesizing biochemical and genetic studies on ODC degradation pathways Cell Cycle Medium 16205122
2003 Crystal structure of Trypanosoma brucei ODC bound to D-ornithine and G418 (2.5-Å resolution) shows D-ornithine forms a Schiff base with the PLP cofactor; the carboxylate binds on the si face of PLP. G418 binds at the boundary between two domains and disorders a 10-residue active-site loop (residues 392–401), providing a mechanism for allosteric inhibition. X-ray crystallography at 2.5-Å resolution with substrate analog and inhibitor The Journal of Biological Chemistry High 12672797
2011 In yeast ODC, an N-terminal unstructured domain (~45 residues, ODS) functions as a transplantable, ubiquitin-independent degron. The unstructured nature (not a specific sequence) is required; ODS can be functionally replaced by an unrelated unstructured domain. Oaz1 binding to ODC monomers is required to activate/expose ODS, and increasing the distance of ODS from the rest of ODC reduces Oaz1-dependence. Extensive mutagenesis; domain-swap experiments; proteasome degradation assays in S. cerevisiae; fusion protein stability assays Journal of Molecular Biology High 21295581
2010 ZNF9 associates with actively translating ribosomes and activates cap-independent (IRES-mediated) translation of human ODC mRNA by directly binding the IRES in the 5′UTR of ODC mRNA. This activity is reduced in primary myoblasts from a DM2 patient. Polyribosome fractionation; direct RNA binding assay; IRES-reporter translation assay in primary human myoblasts including DM2 patient cells PLoS ONE High 20174632
1997 c-Myc/Max heterodimers bind cooperatively to two adjacent E-box sequences (CACGTG) in the first intron of the rat ODC gene, with higher affinity than to a single E-box; cooperative binding of c-Myc/Max to these tandem E-boxes likely contributes to target gene specificity. In vitro DNA binding assay with vaccinia-virus-expressed c-Myc and Max proteins; electrophoretic mobility shift assay with the ODC gene fragment Nucleic Acids Research High 9162900
1997 ODC-transformed cells display constitutive phosphorylation of Sos-1 and Raf-1 (detected as electrophoretic mobility shifts) and constitutive phosphorylation of c-Jun at serines 63 and 73, driven by a kinase distinct from Erk1/2. ODC-transformed cells also show loss of both PDGF α- and β-receptors. Immunoblotting/gel electrophoresis for mobility shifts in NIH3T3 and Rat-1 ODC-transformed cells; comparison with ras- and v-src-transformed cells Oncogene Medium 9365242
1997 Translation initiation factor eIF-4E is required for ODC mRNA translation in ras-transformed cells; antisense suppression of eIF-4E decreases ODC activity and also suppresses polyamine transporter activity, linking ras-induced malignancy to polyamine metabolism through eIF-4E. Antisense eIF-4E expression in CREFT24 ras-transformed rat embryo fibroblasts; measurement of ODC activity and polyamine uptake Biochemical and Biophysical Research Communications Medium 9367873
1990 Superinduction of ODC activity by actinomycin D is due to stimulation of ODC mRNA translation (increased rate of ODC protein synthesis), not to mRNA stabilization; steady-state ODC mRNA levels are unchanged while ODC synthesis rate increases, indicating translational regulation. [35S]methionine incorporation into immunoprecipitated ODC protein; ODC activity assays; RNA quantification in Ehrlich ascites tumor cells FEBS Letters Medium 2384152
2018 A de novo heterozygous gain-of-function nonsense mutation in ODC1 (c.1342 A>T) leads to a C-terminal truncation removing 14 amino acids; the truncated protein is resistant to normal proteasomal degradation, accumulates to high levels, and produces elevated putrescine in patient cells (RBCs and fibroblasts), causing a syndromic neurodevelopmental disorder. Whole-exome sequencing; Sanger sequencing confirmation; red blood cell ODC protein and polyamine level measurement; patient cell biochemistry American Journal of Medical Genetics Part A High 30239107
2019 Primary dermal fibroblasts from a patient with the ODC1 gain-of-function mutation (c.1342 A>T) show 12–17-fold elevated ODC enzyme activity and large accumulation of ODC protein and putrescine; the accumulated truncated ODC protein variant remains enzymatically active. DFMO treatment normalizes ODC activity and putrescine levels without cell toxicity. 14C radioactive ODC enzyme activity assay; ODC protein quantification; putrescine measurement in primary patient-derived fibroblasts and RBCs; DFMO inhibitor treatment The Biochemical Journal High 31249027
1999 Ectopic expression of antizyme induces rapid decline in intracellular polyamines and cell death in both normal and transformed cell lines; antizyme blocks tumor formation in vivo in nude mice, demonstrating that antizyme exerts its anti-tumor activity through ODC inactivation and polyamine depletion. Inducible antizyme expression vector in transformed NIH3T3 cells; nude mouse tumor formation assay; polyamine measurement Oncogene High 9926931
1998 In oral carcinogenesis, reduced/lost expression of ODC antizyme (ODC-Az) leads to elevated ODC mRNA, prolonged ODC protein half-life, and elevated ODC enzymatic activity, demonstrating that loss of antizyme function is a mechanism for ODC deregulation in tumor development. Subtractive hybridization; Northern blot; Southern blot (RFLP); direct ODC enzymatic activity measurement in hamster oral keratinocytes vs. malignant cells Oncogene High 9692545
2021 ODC-dependent putrescine synthesis in macrophages maintains basal expression of MerTK (MER tyrosine-protein kinase) via a histone methylation-dependent transcriptional mechanism; lower basal MerTK in ODC-deficient macrophages impairs MerTK-Erk1/2-dependent IL-10 production upon apoptotic cell exposure, reducing inflammation resolution. RNA-seq of ODC-deficient macrophages; myeloid-specific ODC deletion; zymosan peritonitis model; nanoparticle-mediated ODC silencing; putrescine rescue experiments; Western blotting for MerTK and Erk1/2 signaling Arteriosclerosis, Thrombosis, and Vascular Biology High 33406854
2006 Antizyme overexpression in K14-MEK transgenic skin dramatically delays tumor incidence and reduces tumor multiplicity, primarily by inhibiting putrescine accumulation (putrescine decreased in MEK/AZ tumors while spermidine/spermine unaffected); the mechanism involves slowing cell growth by increasing G2/M transit time rather than inducing apoptosis. Cross-breeding of MEK and antizyme transgenic mice; polyamine measurement; S-phase and mitotic index analysis; TUNEL assay Carcinogenesis High 16400186
2020 FATS (fragile-site associated tumour suppressor) binds to ERβ and translocates to the cytosol, leading to ODC protein degradation; FATS suppresses ODC at both protein and mRNA levels in an ERβ-dependent manner, thereby inhibiting polyamine biosynthesis in NSCLC cells. Co-immunoprecipitation (FATS-ERβ binding); subcellular fractionation; Western blot; ODC mRNA quantification; functional apoptosis assays in NSCLC cells Cell Death & Disease Medium 33037185
2024 Long-term knockdown of astrocytic Odc1 in APP/PS1 Alzheimer's disease mice completely clears Aβ plaques in the hippocampus and switches astrocytes from a reactive to a regenerative active state (characterized by proBDNF expression); ODC1 acts as a bridge between the astrocytic urea cycle and the putrescine-to-GABA conversion pathway. Viral-mediated Odc1 knockdown in astrocytes of APP/PS1 mice; Aβ plaque immunostaining; transcriptomic analysis; proBDNF western blot Molecular Brain Medium 38216963
1995 Two sites of transcription arrest in the murine ODC gene downstream of the transcription start site are identified: Attenuator 1 (Att.1) at +220 near two USF/Myc-Max binding E-boxes (acts as transient pause) and Attenuator 2 (Att.2) at +1590 near a T-stretch (more prolonged arrest); both are modulated by elongation factor TFIIS. Att.2 recognition is an intrinsic property of RNA Pol II, while Att.1 requires an auxiliary factor. In vitro transcription in HeLa nuclear extract; isolated transcription complex elongation assays; promoter-independent transcription with purified RNA Pol II Oncogene High 7537363
2001 NF-κB directly transactivates the ODC gene in HGF-treated tumor cells, as demonstrated by transient transfection of two ODC gene reporter constructs. Transient transfection of ODC promoter-reporter constructs; NF-κB manipulation in HGF-treated carcinoma cell lines Carcinogenesis Medium 15240510
2006 Prolactin induces ODC activity through a protein kinase C delta (PKCδ) pathway without changing ODC mRNA or protein levels; ODC activity in turn upregulates Bcl-2 expression (blocked by DFMO, rescued by putrescine), contributing to anti-apoptotic effects. Bcl-2 does not affect ODC activity or protein levels. PKCδ inhibitor (rottlerin) treatment; ODC activity assay; Western blot for ODC and Bcl-2; DFMO and putrescine rescue experiments in HL-60 cells Apoptosis Medium 16520895
2020 siRNA-mediated knockdown of ODC1 in primary cultured uroepithelial cells causes genome-wide LINE-1 demethylation, induction of LINE-1 transcripts, double-strand DNA breaks, and decreased cell viability, indicating that ODC1 activity is required to maintain DNA methylation homeostasis. siRNA knockdown; LINE-1 methylation assay; LINE-1 RT-qPCR; γH2AX (DSB marker) immunostaining; cell viability assay in primary uroepithelial cells Scientific Reports Medium 32123240

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1989 Prevention of rapid intracellular degradation of ODC by a carboxyl-terminal truncation. Science (New York, N.Y.) 229 2928784
2008 ODC1 is a critical determinant of MYCN oncogenesis and a therapeutic target in neuroblastoma. Cancer research 218 19047152
2001 A novel transformation suppressor, Pdcd4, inhibits AP-1 transactivation but not NF-kappaB or ODC transactivation. Oncogene 169 11314000
2004 Polyamines regulate their synthesis by inducing expression and blocking degradation of ODC antizyme. The EMBO journal 110 15538383
2004 Hepatocyte growth factor-activated NF-kappaB regulates HIF-1 activity and ODC expression, implicated in survival, differently in different carcinoma cell lines. Carcinogenesis 99 15240510
1991 Effects of overexpression of ornithine decarboxylase (ODC) on growth control and oncogene-induced cell transformation. Oncogene 93 1711188
1984 Polyamines and intestinal growth: absolute requirement for ODC activity in adaptation during lactation. The American journal of physiology 82 6437251
1995 L-glutamine and L-asparagine stimulate ODC activity and proliferation in a porcine jejunal enterocyte line. The American journal of physiology 72 7485512
1999 Anti-tumor activity of antizyme which targets the ornithine decarboxylase (ODC) required for cell growth and transformation. Oncogene 71 9926931
1997 c-Myc/Max heterodimers bind cooperatively to the E-box sequences located in the first intron of the rat ornithine decarboxylase (ODC) gene. Nucleic acids research 69 9162900
1996 The ornithine decarboxylase gene odc is required for alcaligin siderophore biosynthesis in Bordetella spp.: putrescine is a precursor of alcaligin. Journal of bacteriology 67 8550442
1989 Cholecystokinin and gastrin peptides stimulate ODC activity in a rat pancreatic cell line. The American journal of physiology 65 2719109
1988 Dissociation of c-fos from ODC expression and neuronal differentiation in a PC12 subline stably transfected with an inducible N-ras oncogene. Biochemical and biophysical research communications 65 3277634
2000 Inhibition of ornithine decarboxylase (ODC) decreases tumor vascularization and reverses spontaneous tumors in ODC/Ras transgenic mice. Cancer research 60 11059762
1975 Regulation of thyroid ornithine ornithine decarboxylase (ODC) by thyrotropin. I. The rat. Endocrinology 60 165059
2000 K6/ODC transgenic mice as a sensitive model for carcinogen identification. Toxicology letters 50 10906419
2018 Novel de novo pathogenic variant in the ODC1 gene in a girl with developmental delay, alopecia, and dysmorphic features. American journal of medical genetics. Part A 49 30239107
2012 Glutamatergic GRIN2B and polyaminergic ODC1 genes in suicide attempts: associations and gene-environment interactions with childhood/adolescent physical assault. Molecular psychiatry 48 22850629
2005 Mechanisms of protein degradation: an odyssey with ODC. Cell cycle (Georgetown, Tex.) 46 16205122
1984 The role of mitogens and lymphokines in the induction of ornithine decarboxylase (ODC) in T lymphocytes. Journal of immunology (Baltimore, Md. : 1950) 46 6229581
2013 Quantitative analysis of BTF3, HINT1, NDRG1 and ODC1 protein over-expression in human prostate cancer tissue. PloS one 44 24386364
2021 ODC (Ornithine Decarboxylase)-Dependent Putrescine Synthesis Maintains MerTK (MER Tyrosine-Protein Kinase) Expression to Drive Resolution. Arteriosclerosis, thrombosis, and vascular biology 43 33406854
1992 Polyamine levels, ornithine decarboxylase (ODC) activity, and ODC-mRNA expression in normal and cancerous human colonocytes. Life sciences 42 1573975
1997 Translation of ODC mRNA and polyamine transport are suppressed in ras-transformed CREF cells by depleting translation initiation factor 4E. Biochemical and biophysical research communications 39 9367873
2003 X-ray structure determination of Trypanosoma brucei ornithine decarboxylase bound to D-ornithine and to G418: insights into substrate binding and ODC conformational flexibility. The Journal of biological chemistry 38 12672797
1995 Life-long over-expression of ornithine decarboxylase (ODC) gene in transgenic mice does not lead to generally enhanced tumorigenesis or neuronal degeneration. International journal of cancer 37 7591239
2018 Gain-of-function variants in the ODC1 gene cause a syndromic neurodevelopmental disorder associated with macrocephaly, alopecia, dysmorphic features, and neuroimaging abnormalities. American journal of medical genetics. Part A 36 30475435
2005 Haploinsufficiency for odc modifies mouse skin tumor susceptibility. Cancer research 36 15734996
2011 The N-terminal unstructured domain of yeast ODC functions as a transplantable and replaceable ubiquitin-independent degron. Journal of molecular biology 35 21295581
2016 Targeting ODC1 inhibits tumor growth through reduction of lipid metabolism in human hepatocellular carcinoma. Biochemical and biophysical research communications 34 27592554
2013 Critical roles of Myc-ODC axis in the cellular transformation induced by myeloproliferative neoplasm-associated JAK2 V617F mutant. PloS one 34 23300995
2017 Extracellular polyamines-induced proliferation and migration of cancer cells by ODC, SSAT, and Akt1-mediated pathway. Anti-cancer drugs 33 28157137
2005 Factors associated with variation in bulk-tank-milk Salmonella Dublin ELISA ODC% in dairy herds. Preventive veterinary medicine 33 15820114
2000 Sequence, expression and functional analysis of the Coccidioides immitis ODC (ornithine decarboxylase) gene. Gene 32 10721738
1998 Effects of 50 Hz magnetic fields on UV-induced skin tumourigenesis in ODC-transgenic and non-transgenic mice. International journal of radiation biology 32 9464483
2019 ODC1 promotes proliferation and mobility via the AKT/GSK3β/β-catenin pathway and modulation of acidotic microenvironment in human hepatocellular carcinoma. OncoTargets and therapy 31 31239700
2018 ODC1 inhibits the inflammatory response and ROS-induced apoptosis in macrophages. Biochemical and biophysical research communications 31 30217446
2006 Tumor suppressor activity of ODC antizyme in MEK-driven skin tumorigenesis. Carcinogenesis 31 16400186
2017 Herbacetin suppresses cutaneous squamous cell carcinoma and melanoma cell growth by targeting AKT and ODC. Carcinogenesis 29 29029040
2010 Life without putrescine: disruption of the gene-encoding polyamine oxidase in Ustilago maydis odc mutants. FEMS yeast research 29 20840600
1999 DNA damage, cell kinetics and ODC activities studied in CBA mice exposed to electromagnetic fields generated by transmission lines. In vivo (Athens, Greece) 29 10757046
1993 Spermidine-induced destabilization of ornithine decarboxylase (ODC) is mediated by accumulation of antizyme in ODC-overproducing variant cells. The Journal of biological chemistry 28 8486633
1998 Trypanosoma brucei brucei: characterization of an ODC null bloodstream form mutant and the action of alpha-difluoromethylornithine. Experimental parasitology 27 9562432
2010 ZNF9 activation of IRES-mediated translation of the human ODC mRNA is decreased in myotonic dystrophy type 2. PloS one 26 20174632
2001 Amplification of Mycn, Ddx1, Rrm2, and Odc1 in rat uterine endometrial carcinomas. Genes, chromosomes & cancer 26 11433525
2021 Emerging Role of ODC1 in Neurodevelopmental Disorders and Brain Development. Genes 25 33806076
1998 Analysis of ras gene mutational spectra in epidermal papillomas from K6/ODC transgenic mice. Molecular carcinogenesis 25 9688139
1997 Cells transformed by ODC, c-Ha-ras and v-src exhibit MAP kinase/Erk-independent constitutive phosphorylation of Sos, Raf and c-Jun activation domain, and reduced PDGF receptor expression. Oncogene 25 9365242
2017 Targeting ornithine decarboxylase (ODC) inhibits esophageal squamous cell carcinoma progression. NPJ precision oncology 24 29872701
2006 Increasing ornithine decarboxylase activity is another way of prolactin preventing methotrexate-induced apoptosis: crosstalk between ODC and BCL-2. Apoptosis : an international journal on programmed cell death 23 16520895
2000 Expression of ODC and its regulatory protein antizyme in the adult rat brain. Journal of neuroscience research 23 11104505
1998 Reduction of ornithine decarboxylase antizyme (ODC-Az) level in the 7,12-dimethylbenz(a)anthracene-induced hamster buccal pouch carcinogenesis model. Oncogene 22 9692545
1997 Polyamine levels and ODC activity in intestinal-type and diffuse-type gastric carcinoma. Digestive diseases and sciences 22 9073141
1993 Isolation and characterization of the Drosophila ornithine decarboxylase locus: evidence for the presence of two transcribed ODC genes in the Drosophila genome. DNA and cell biology 22 8329117
1988 Cloning of the orotidine 5'-phosphate decarboxylase (ODC) gene of Schwanniomyces occidentalis by complementation of the ura3 mutation in S. cerevisiae. Current genetics 22 2834102
2011 A prolonged and exaggerated wound response with elevated ODC activity mimics early tumor development. Carcinogenesis 20 21730362
2004 Elevated polyamines lead to selective induction of apoptosis and inhibition of tumorigenesis by (-)-epigallocatechin-3-gallate (EGCG) in ODC/Ras transgenic mice. Carcinogenesis 20 15375010
1990 Superinduction of ornithine decarboxylase (ODC) by actinomycin D is due to stimulation of ODC mRNA translation. FEBS letters 20 2384152
1989 GFR increases before renal mass or ODC activity increase in rats fed high protein diets. Kidney international 20 2593487
2019 Biochemical features of primary cells from a pediatric patient with a gain-of-function ODC1 genetic mutation. The Biochemical journal 19 31249027
2019 SKP2, positively regulated by circ_ODC1/miR-422a axis, promotes the proliferation of retinoblastoma. Journal of cellular biochemistry 19 31297892
1989 Effect of Na + flux inhibitors on induction of c-fos, c-myc, and ODC genes during cell cycle. Journal of cellular physiology 19 2472417
2016 Expression of ODC Antizyme Inhibitor 2 (AZIN2) in Human Secretory Cells and Tissues. PloS one 18 26963840
2005 Ornithine decarboxylase (ODC) expression pattern in human prostate tissues and ODC transgenic mice. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 18 16234506
2001 Retinoic acid (RA) receptor transcriptional activation correlates with inhibition of 12-O-tetradecanoylphorbol-13-acetate-induced ornithine decarboxylase (ODC) activity by retinoids: a potential role for trans-RA-induced ZBP-89 in ODC inhibition. International journal of cancer 18 11149424
2022 Downregulation of MTAP promotes Tumor Growth and Metastasis by regulating ODC Activity in Breast Cancer. International journal of biological sciences 17 35541910
2015 Bag-1 promotes cell survival through c-Myc-mediated ODC upregulation that is not preferred under apoptotic stimuli in MCF-7 cells. Cell biochemistry and function 17 26178413
1989 Linkage genetics of mouse ornithine decarboxylase (Odc). Genomics 17 2575591
2021 Effects of ODC on polyamine metabolism, hormone levels, cell proliferation and apoptosis in goose ovarian granulosa cells. Poultry science 16 34175802
2017 Expression of ODC1, SPD, SPM and AZIN1 in the hypothalamus, ovary and uterus during rat estrous cycle. General and comparative endocrinology 16 28315656
2016 Simultaneous targeting of 5-LOX-COX and ODC block NNK-induced lung adenoma progression to adenocarcinoma in A/J mice. American journal of cancer research 16 27293987
2006 Modest increase in temperature affects ODC activity in L929 cells: Low-level radiofrequency radiation does not. Radiation and environmental biophysics 16 16850337
2016 Plasmodium AdoMetDC/ODC bifunctional enzyme is essential for male sexual stage development and mosquito transmission. Biology open 15 27387533
1991 Postnatal developmental changes in inner ear ornithine decarboxylase (ODC). Hearing research 15 1752793
2024 Long-term inhibition of ODC1 in APP/PS1 mice rescues amyloid pathology and switches astrocytes from a reactive to active state. Molecular brain 14 38216963
1989 Human ornithine decarboxylase(ODC)-encoding gene: cloning and expression in ODC-deficient CHO cells. Gene 14 2556329
1988 Identification of an X-linked member of the Odc gene family in the mouse. Nucleic acids research 14 3347509
2020 Basic Hallmarks of Urothelial Cancer Unleashed in Primary Uroepithelium by Interference with the Epigenetic Master Regulator ODC1. Scientific reports 13 32123240
2017 Putrescine independent wound response phenotype is produced by ODC-like RNAi in planarians. Scientific reports 13 28851936
2005 Regional and temporal alterations of ODC/polyamine system during ALS-like neurodegenerative motor syndrome in G93A transgenic mice. Neurochemistry international 13 16290266
1992 Developmental regulation of ornithine decarboxylase (ODC) in rat testis: comparison of changes in ODC activity with changes in ODC mRNA levels during testicular maturation. Biology of reproduction 13 1576258
1988 A functional mouse ornithine decarboxylase gene (Odc) maps to chromosome 12: further evidence of homoeology between mouse chromosome 12 and the short arm of human chromosome 2. Cytogenetics and cell genetics 13 3197454
2020 Increased putrescine levels due to ODC1 overexpression prevents mitochondrial dysfunction-related apoptosis induced by methylmercury. Life sciences 12 32615186
2017 Overexpression of mitochondrial oxodicarboxylate carrier (ODC1) preserves oxidative phosphorylation in a yeast model of Barth syndrome. Disease models & mechanisms 12 28188263
2012 RNAi-mediated down-regulation of ornithine decarboxylase (ODC) impedes wound-stress stimulation of anabasine synthesis in Nicotiana glauca. Phytochemistry 12 23177980
1997 Catecholamines are required for androgen-induced ODC expression but not for hypertrophy of mouse kidney. Biochimica et biophysica acta 12 9194572
2024 Elevated expression of HIGD1A drives hepatocellular carcinoma progression by regulating polyamine metabolism through c-Myc-ODC1 nexus. Cancer & metabolism 11 38395945
2007 Folate deficiency enhances arsenic effects on expression of genes involved in epidermal differentiation in transgenic K6/ODC mouse skin. Toxicology 11 17928125
2015 TP53 modulating agent, CP-31398 enhances antitumor effects of ODC inhibitor in mouse model of urinary bladder transitional cell carcinoma. American journal of cancer research 10 26693057
2006 Polyamine analogs with xylene rings induce antizyme frameshifting, reduce ODC activity, and deplete cellular polyamines. Journal of biochemistry 10 16998202
1995 Transcription elongation of the murine ornithine decarboxylase (ODC) gene is regulated in vitro at two downstream elements by different attenuation mechanisms. Oncogene 10 7537363
1993 ODC activity and polyamine levels in isolated human colonocytes. Life sciences 10 8366761
1990 Differential effects of sex steroids on uterine and renal ODC activity in ovariectomized rats. Life sciences 10 2243540
2020 FATS regulates polyamine biosynthesis by promoting ODC degradation in an ERβ-dependent manner in non-small-cell lung cancer. Cell death & disease 9 33037185
2011 Isolation, characterization and expression analysis of the ornithine decarboxylase gene (ODC1) of the entomopathogenic fungus, Metarhizium anisopliae. Microbiological research 9 21236653
2009 Targeted antitumor effect induced by hTERT promoter mediated ODC antisense adenovirus. Molecular biology reports 9 19876766
2006 Adenovirus-mediated expression of both antisense ODC and AdoMetDC inhibited colorectal cancer cell growth in vitro. Acta pharmacologica Sinica 9 16490173
1992 Activity of ornithine decarboxylase (ODC) and polyamine levels as biochemical markers of malignancy in human brain tumors. Acta histochemica. Supplementband 9 1584960
1986 Aging in the AXC/SSh rat: diminished prostate L-ornithine decarboxylase (ODC) activity reflects diminished prostate ODC protein and transcript content. Endocrinology 9 2428603
2018 TAAR1 induces a disturbed GSK3β phosphorylation in recurrent miscarriages through the ODC. Endocrine connections 8 29472377