PUBLICATION
cDNA cloning of human retinoic acid-metabolizing enzyme (hP450RAI) identifies a novel family of cytochromes P450
- Authors
- White, J.A., Beckett-Jones, B., Guo, Y.D., Dilworth, F.J., Bonasoro, J., Jones, G., and Petkovich, M.
- ID
- ZDB-PUB-971204-4
- Date
- 1997
- Source
- The Journal of biological chemistry 272(30): 18538-18541 (Journal)
- Registered Authors
- Guo, Yaling, Petkovich, Martin
- Keywords
- none
- MeSH Terms
-
- Amino Acid Sequence
- Animals
- COS Cells
- Cloning, Molecular
- Conserved Sequence
- Cytochrome P-450 Enzyme System/genetics*
- Cytochrome P-450 Enzyme System/metabolism
- DNA, Complementary/genetics
- DNA, Complementary/metabolism
- Humans
- Mixed Function Oxygenases/genetics*
- Mixed Function Oxygenases/metabolism
- Molecular Sequence Data
- RNA, Messenger/metabolism
- Sequence Alignment
- Tretinoin/metabolism*
- Zebrafish
- PubMed
- 9228017 Full text @ J. Biol. Chem.
Citation
White, J.A., Beckett-Jones, B., Guo, Y.D., Dilworth, F.J., Bonasoro, J., Jones, G., and Petkovich, M. (1997) cDNA cloning of human retinoic acid-metabolizing enzyme (hP450RAI) identifies a novel family of cytochromes P450. The Journal of biological chemistry. 272(30):18538-18541.
Abstract
Retinoids, including all-trans-retinoic acid (RA) and its stereoisomer 9-cis-RA play important roles in regulating gene expression, through interactions with nuclear receptors, during embryonic development and in the maintenance of adult epithelial tissues (Chambon, P. (1995) Rec. Prog. Horm. Res. 50, 317-32; Mangelsdorf, D. J., and Evans, R. M. (1995) Cell 83, 841-850; Petkovich, M. (1992) Annu. Rev. Nutr. 12, 443-471). Evidence suggests that 4-hydroxylation of RA inside the target cell limits its biological activity and initiates a degradative process of RA leading to its eventual elimination. However, 18-hydroxylation and glucuronidation may also be important steps in this process. In this paper, we describe the cloning and characterization of the first mammalian retinoic acid-inducible retinoic acid-metabolizing cytochrome P450 (hP450RAI), which belongs to a novel class of cytochromes (CYP26). We demonstrate that hP450RAI is responsible for generation of several hydroxylated forms of RA, including 4-OH-RA, 4-oxo-RA, and 18-OH-RA. We also show that hP450RAI mRNA expression is highly induced by RA in certain human tumor cell lines and further show that RA-inducible RA metabolism may correlate with P450RAI expression. We conclude that this enzyme plays a key role in RA metabolism, functioning in a feedback loop where RA levels are controlled in an autoregulatory manner.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping