TY - JOUR
T1 - Cloning and characterization of a human polyamine oxidase that is inducible by polyamine analogue exposure
AU - Wang, Yanlin
AU - Devereux, Wendy
AU - Woster, Patrick M.
AU - Stewart, Tracy Murray
AU - Hacker, Amy
AU - Casero, Robert A.
PY - 2001/7/15
Y1 - 2001/7/15
N2 - Mammalian polyamine catabolism is under the control of two enzymes, spermidine/spermine N1-acetyltransferase and the flavin adenine dinucleotide-dependent polyamine oxidase (PAO). In this study, the cloning and initial characterization of human PAO is reported. A 1894-bp cDNA with an open reading frame of 1668-bp codes for a protein of 555 amino acids. In vitro transcription/translation of this cDNA clone produces the expected Mr 61, 900 protein with PAO activity. The PAO activity of this clone is inhibited by MDL 72, 527, a specific inhibitor of mammalian PAO. However, neither pargyline, a specific monoamine oxidase inhibitor, nor semicarbazide, a specific diamine oxidase inhibitor, inhibits the PAO activity of this clone. PAO has been referred to as being constitutively expressed. However, 24-h exposure of a non-small cell lung carcinoma cell line, NCI H157, to 10 μM of N1, N″-bis(ethyl)norspermine results in ∼5-fold induction of PAO mRNA and a > 3-fold induction of PAO activity. These results demonstrate that in at least one cell type, PAO is up-regulated in response to polyamine analogue exposure. The PAO clone described here should provide a useful tool, which will facilitate the dissection of the role of polyamine catabolism in normal growth and in response to the antitumor polyamine analogues.
AB - Mammalian polyamine catabolism is under the control of two enzymes, spermidine/spermine N1-acetyltransferase and the flavin adenine dinucleotide-dependent polyamine oxidase (PAO). In this study, the cloning and initial characterization of human PAO is reported. A 1894-bp cDNA with an open reading frame of 1668-bp codes for a protein of 555 amino acids. In vitro transcription/translation of this cDNA clone produces the expected Mr 61, 900 protein with PAO activity. The PAO activity of this clone is inhibited by MDL 72, 527, a specific inhibitor of mammalian PAO. However, neither pargyline, a specific monoamine oxidase inhibitor, nor semicarbazide, a specific diamine oxidase inhibitor, inhibits the PAO activity of this clone. PAO has been referred to as being constitutively expressed. However, 24-h exposure of a non-small cell lung carcinoma cell line, NCI H157, to 10 μM of N1, N″-bis(ethyl)norspermine results in ∼5-fold induction of PAO mRNA and a > 3-fold induction of PAO activity. These results demonstrate that in at least one cell type, PAO is up-regulated in response to polyamine analogue exposure. The PAO clone described here should provide a useful tool, which will facilitate the dissection of the role of polyamine catabolism in normal growth and in response to the antitumor polyamine analogues.
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M3 - Article
C2 - 11454677
AN - SCOPUS:0035878846
SN - 0008-5472
VL - 61
SP - 5370
EP - 5373
JO - Cancer Research
JF - Cancer Research
IS - 14
ER -