Retinoids, particularly all-trans-retinoic acid (RA), are potent regulators of cell differentiation, cell proliferation, and apoptosis. The role of all-trans-RA during development and in the maintenance of adult tissues has been well established. The control of all-trans-RA levels in cells and tissues is regulated by the balance between its biosynthesis and its catabolism to inactive metabolites. The cytochrome P450 enzyme P450RAI (herein renamed P450RAI-1) is partially responsible for this inactivation of all-trans-RA. In this report, we describe the identification, molecular cloning, and characterization of a second related enzyme, P450RAI-2, which is also involved in the specific inactivation of all-trans-RA. Transiently transfected P450RAI-2 can convert all-trans-RA to more polar metabolites including 4-oxo-, 4-OH-, and 18-OH-all-trans-RA. Competition experiments with other retinoids suggest that all-trans-RA is the preferred substrate. The high level of expression of P450RAI-2, particularly in the cerebellum and pons of human adult brain, suggests a unique role for this enzyme in the protection of specific tissues from exposure to retinoids.
| Predicate | Object |
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| rdf:type | |
| rdfs:comment |
Retinoids, particularly all-trans-retinoic acid (RA), are potent regulators of cell differentiation, cell proliferation, and apoptosis. The role of all-trans-RA during development and in the maintenance of adult tissues has been well established. The control of all-trans-RA levels in cells and tissues is regulated by the balance between its biosynthesis and its catabolism to inactive metabolites. The cytochrome P450 enzyme P450RAI (herein renamed P450RAI-1) is partially responsible for this inactivation of all-trans-RA. In this report, we describe the identification, molecular cloning, and characterization of a second related enzyme, P450RAI-2, which is also involved in the specific inactivation of all-trans-RA. Transiently transfected P450RAI-2 can convert all-trans-RA to more polar metabolites including 4-oxo-, 4-OH-, and 18-OH-all-trans-RA. Competition experiments with other retinoids suggest that all-trans-RA is the preferred substrate. The high level of expression of P450RAI-2, particularly in the cerebellum and pons of human adult brain, suggests a unique role for this enzyme in the protection of specific tissues from exposure to retinoids.
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| skos:exactMatch | |
| uniprot:name |
Proc. Natl. Acad. Sci. U.S.A.
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| uniprot:author |
Creighton S.,
Everingham S.,
Jones G.,
Petkovich M.,
Ramshaw H.,
Stangle W.,
Taimi M.,
Tam S.-P.,
White J.A.,
Zhang A.
|
| uniprot:date |
2000
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| uniprot:pages |
6403-6408
|
| uniprot:title |
Identification of the human cytochrome P450, P450RAI-2, which is predominantly expressed in the adult cerebellum and is responsible for all-trans-retinoic acid metabolism.
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| uniprot:volume |
97
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| dc-term:identifier |
doi:10.1073/pnas.120161397
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