Literature summary for 4.1.1.17 extracted from

Shantz, L.M.; Levin, V.A.
Regulation of ornithine decarboxylase during oncogenic transformation: mechanisms and therapeutic potential (2007), Amino Acids, 33, 213-223.

Activating Compound

Activating Compound	Comment	Organism
additional information	ODC induction, e.g. in response to the tumor promoter 12-O-tetradecanoylphorbol-13-acetate, is a necessary step in MEK-induced tumorigenesis, ODC is induced during carcinogenesis by a variety of oncogenic stimuli, overview	Mus musculus
additional information	ODC induction, e.g. in response to the tumor promoter 12-O-tetradecanoylphorbol-13-acetate, is a necessary step in MEK-induced tumorigenesis, ODC is induced during carcinogenesis by a variety of oncogenic stimuli, overview	Rattus norvegicus
additional information	ODC induction, e.g. in response to the tumor promoter 12-O-tetradecanoylphorbol-13-acetate, is a necessary step in MEK-induced tumorigenesis, overview, ODC is induced during carcinogenesis by a variety of oncogenic stimuli, ODC activity is induced in cells that overexpress the translation initiation factor eIF4E, overview	Homo sapiens

Application

Application	Comment	Organism
diagnostics	a single nucleotide polymorphism in intron 1 of the ODC gene serves as genetic marker for colon cancer	Homo sapiens
drug development	the enzyme ODC is a drug target in human malignancies, such as skin cancer	Homo sapiens
pharmacology	the enzyme ODC is possibly useful in chemotherapy of human malignancies, such as skin cancer	Homo sapiens

Cloned(Commentary)

Cloned (Comment)	Organism
expression of ODC in transgenic mice or rats leading to altered, tumoric skin phenotypes, overview, a single nucleotide polymorphism occurs in intron 1 of the ODC gene, which results in increased ODC expression in response to Myc, expression in NIH-3T3 cells overexpressing eIF4E, alpha-difluoromethylornithine not only inhibits proliferation, but also reverts the transformed phenotype of NIH-3T3 cells overexpressing eIF4E	Homo sapiens

Cloned (Comment)

Organism

expression of ODC in transgenic mice or rats leading to altered, tumoric skin phenotypes, overview, a single nucleotide polymorphism occurs in intron 1 of the ODC gene, which results in increased ODC expression in response to Myc, expression in NIH-3T3 cells overexpressing eIF4E, alpha-difluoromethylornithine not only inhibits proliferation, but also reverts the transformed phenotype of NIH-3T3 cells overexpressing eIF4E

Homo sapiens

Protein Variants

Protein Variants	Comment	Organism
additional information	ODC transgenic rodent models of skin carcinogenesis, phenotypes, overview	Homo sapiens
additional information	transgenic mice overexpressing ODC in hair follicle keratinocytes using keratin promotors are much more sensitive than littermate controls to DMBA-induced carcinogenesis, and do not require treatment with a tumor promoter to develop tumors, overview	Mus musculus

General Stability

General Stability	Organism
the wild type form of ODC has an extremely short half life of 20-30 min, and its degradation is mediated by antizyme, which binds to the monomeric form of ODC, preventing formation of the enzymatically active homodimer, and then targets ODC for degradation	Mus musculus
the wild type form of ODC has an extremely short half life of 20-30 min, and its degradation is mediated by antizyme, which binds to the monomeric form of ODC, preventing formation of the enzymatically active homodimer, and then targets ODC for degradation	Homo sapiens
the wild type form of ODC has an extremely short half life of 20-30 min, and its degradation is mediated by antizyme, which binds to the monomeric form of ODC, preventing formation of the enzymatically active homodimer, and then targets ODC for degradation	Rattus norvegicus

Inhibitors

Inhibitors	Comment	Organism
alpha-difluoromethylornithine	i.e. DFMO, irreversible inactivator, physiologic effects, e.g. causes arrest in G1 phase in neuroblastoma cells, the cytostatic effect is reversible by putrescine, overview, acts synergistically with SAM486A, MDL-73811, cisplatin, and 5-fluorouracil	Homo sapiens
alpha-difluoromethylornithine	i.e. DFMO, irreversible inactivator, antitumor action of ODC inhibition using DFMO, chemopreventive effects, DFMO provides significant protection against N-butyl-N(4-hydroxybutyl)-nitrosamine-induced bladder cancer, overview	Mus musculus
alpha-difluoromethylornithine	i.e. DFMO, irreversible inactivator, antitumor action of ODC inhibition using DFMO, chemopreventive effects, DFMO provides significant protection against 7,12-dimethylbenz[a]-anthracene-induced mammary carcinogenesis, overview	Rattus norvegicus
antizyme	an important endogenous regulator of ODC and polyamine homeostasis, overview, the wild type form of ODC has an extremely short half life of 20-30 min, and its degradation is mediated by antizyme, which binds to the monomeric form of ODC, preventing formation of the enzymatically active homodimer, and then targets ODC for degradation	Homo sapiens
antizyme	an important endogenous regulator of ODC and polyamine homeostasis, overview, the wild type form of ODC has an extremely short half life of 20-30 min, and its degradation is mediated by antizyme, which binds to the monomeric form of ODC, preventing formation of the enzymatically active homodimer, and then targets ODC for degradation	Mus musculus
antizyme	an important endogenous regulator of ODC and polyamine homeostasis, overview, the wild type form of ODC has an extremely short half life of 20-30 min, and its degradation is mediated by antizyme, which binds to the monomeric form of ODC, preventing formation of the enzymatically active homodimer, and then targets ODC for degradation	Rattus norvegicus
additional information	the enzyme is induced by phorbol esters, rapamycin, which blocks phosphorylation of 4E-BP1, inhibits the induction of ODC in response to serum	Homo sapiens
additional information	inhibition of ODC activity reverts the transformation of cells in vitro and reduces tumor growth	Mus musculus
additional information	inhibition of ODC activity reverts the transformation of cells in vitro and reduces tumor growth	Rattus norvegicus

Natural Substrates/ Products (Substrates)

Natural Substrates	Organism	Comment (Nat. Sub.)	Natural Products	Comment (Nat. Pro.)	Rev.
L-ornithine	Rattus norvegicus	first enzyme in polyamine biosynthesis, the unique and tight regulation of the enzyme occurs at the levels of transcription, translation and protein degradation, dysregulation of ornithine decarboxylase during oncogenic transformation regulation occurs at the levels of transcription, translation and protein degradation, mechanisms and therapeutic potential, overview, ODC induction as a necessary step in MEK-induced tumorigenesis, enzyme inhibition reduces tumor growth, synergistic or additive effects with vindesine or doxorubicin, overview	putrescine + CO2	-	?
L-ornithine	Homo sapiens	first enzyme in polyamine biosynthesis, the unique and tight regulation of the enzyme occurs at the levels of transcription, translation and protein degradation, dysregulation of ornithine decarboxylase during oncogenic transformation regulation occurs at the levels of transcription, translation and protein degradation, mechanisms, e.g. via the Ras effector pathways, and therapeutic potential, overview, ODC induction as a necessary step in MEK-induced tumorigenesis, enzyme inhibition reduces tumor growth, synergistic or additive effects, overview	putrescine + CO2	-	?
L-ornithine	Mus musculus	first enzyme in polyamine biosynthesis, the unique and tight regulation of the enzyme occurs at the levels of transcription, translation and protein degradation, dysregulation of ornithine decarboxylase during oncogenic transformation, mechanisms and therapeutic potential, overview, ODC induction as a necessary step in MEK-induced tumorigenesis, enzyme inhibition reduces tumor growth, synergistic or additive effects with vindesine or doxorubicin, overview	putrescine + CO2	-	?
additional information	Mus musculus	the Raf/MEK/ERK pathway is involved in the regulation of ODC during skin tumorigenesis, overview	?	-	?
additional information	Rattus norvegicus	the Raf/MEK/ERK pathway is involved in the regulation of ODC during skin tumorigenesis, overview	?	-	?
additional information	Homo sapiens	the Raf/MEK/ERK pathway is involved in the regulation of ODC during skin tumorigenesis, the Raf/MEK/ERK cascade mediates ODC transcription and the PI 3-kinase cascade mediates ODC translation, overview, a single nucleotide polymorphism occurs in intron 1 of the ODC gene, which results in increased ODC expression in response to Myc	?	-	?

Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	-	-	-
Mus musculus	-	MEK mutant K14-MEK mice	-
Rattus norvegicus	-	-	-

Source Tissue

Source Tissue	Comment	Organism	Textmining
AR4-2J cell	AR4-2J pancreatic tumor cells, which show increased phosphorylation of the eIF4E regulatory protein 4E-BP1 and high levels of eIF4E compared to normal cells, also exhibit increased translational initiation of ODC mRNA	Rattus norvegicus	-
B-16 cell	melanoma cell line	Mus musculus	-
COLO-357 cell	-	Homo sapiens	-
hepatoma cell	-	Homo sapiens	-
hepatoma cell	-	Rattus norvegicus	-
IEC-6 cell	intestinal epithelial cells	Rattus norvegicus	-
intestine	-	Rattus norvegicus	-
L-1210 cell	leukemia cell line	Mus musculus	-
LAN-1 cell	neuroblastoma cell line	Homo sapiens	-
Lewis lung carcinoma cell	-	Mus musculus	-
melanoma cell	-	Homo sapiens	-
neuroblastoma cell	-	Homo sapiens	-
NMB-7 cell	neuroblastoma cell line	Homo sapiens	-
PANC-1 cell	-	Homo sapiens	-
pancreas	-	Homo sapiens	-
pancreatic cancer cell	-	Homo sapiens	-
renal cell carcinoma cell	-	Homo sapiens	-
skin	-	Mus musculus	-
skin	-	Homo sapiens	-
skin	-	Rattus norvegicus	-
small cell lung carcinoma cell	-	Mus musculus	-

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.
L-ornithine	-	Mus musculus	putrescine + CO2	-	?
L-ornithine	-	Homo sapiens	putrescine + CO2	-	?
L-ornithine	-	Rattus norvegicus	putrescine + CO2	-	?
L-ornithine	first enzyme in polyamine biosynthesis, the unique and tight regulation of the enzyme occurs at the levels of transcription, translation and protein degradation, dysregulation of ornithine decarboxylase during oncogenic transformation regulation occurs at the levels of transcription, translation and protein degradation, mechanisms and therapeutic potential, overview, ODC induction as a necessary step in MEK-induced tumorigenesis, enzyme inhibition reduces tumor growth, synergistic or additive effects with vindesine or doxorubicin, overview	Rattus norvegicus	putrescine + CO2	-	?
L-ornithine	first enzyme in polyamine biosynthesis, the unique and tight regulation of the enzyme occurs at the levels of transcription, translation and protein degradation, dysregulation of ornithine decarboxylase during oncogenic transformation regulation occurs at the levels of transcription, translation and protein degradation, mechanisms, e.g. via the Ras effector pathways, and therapeutic potential, overview, ODC induction as a necessary step in MEK-induced tumorigenesis, enzyme inhibition reduces tumor growth, synergistic or additive effects, overview	Homo sapiens	putrescine + CO2	-	?
L-ornithine	first enzyme in polyamine biosynthesis, the unique and tight regulation of the enzyme occurs at the levels of transcription, translation and protein degradation, dysregulation of ornithine decarboxylase during oncogenic transformation, mechanisms and therapeutic potential, overview, ODC induction as a necessary step in MEK-induced tumorigenesis, enzyme inhibition reduces tumor growth, synergistic or additive effects with vindesine or doxorubicin, overview	Mus musculus	putrescine + CO2	-	?
additional information	the Raf/MEK/ERK pathway is involved in the regulation of ODC during skin tumorigenesis, overview	Mus musculus	?	-	?
additional information	the Raf/MEK/ERK pathway is involved in the regulation of ODC during skin tumorigenesis, overview	Rattus norvegicus	?	-	?
additional information	the Raf/MEK/ERK pathway is involved in the regulation of ODC during skin tumorigenesis, the Raf/MEK/ERK cascade mediates ODC transcription and the PI 3-kinase cascade mediates ODC translation, overview, a single nucleotide polymorphism occurs in intron 1 of the ODC gene, which results in increased ODC expression in response to Myc	Homo sapiens	?	-	?

Subunits

Subunits	Comment	Organism
dimer	antizyme binds to the monomeric form of ODC, preventing formation of the enzymatically active homodimer, and then targets ODC for degradation	Mus musculus
dimer	antizyme binds to the monomeric form of ODC, preventing formation of the enzymatically active homodimer, and then targets ODC for degradation	Homo sapiens
dimer	antizyme binds to the monomeric form of ODC, preventing formation of the enzymatically active homodimer, and then targets ODC for degradation	Rattus norvegicus

Synonyms

Synonyms	Comment	Organism
ODC	-	Mus musculus
ODC	-	Homo sapiens
ODC	-	Rattus norvegicus

Cofactor

Cofactor	Comment	Organism
pyridoxal 5'-phosphate	-	Mus musculus
pyridoxal 5'-phosphate	-	Homo sapiens
pyridoxal 5'-phosphate	-	Rattus norvegicus