cDNA克隆人类视黄acid-metabolizing酶(hP450RAI)确定一种新型细胞色素P450的家庭。
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白色的农协,Beckett-Jones B,郭码,:帝尔沃斯历史学FJ, Bonasoro J,琼斯G, Petkovich M
cDNA克隆人类视黄acid-metabolizing酶(hP450RAI)确定一种新型细胞色素P450的家庭。
J生物化学杂志。1997年7月25日,272 (30):18538 - 41。
- PubMed ID
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9228017 (在PubMed]
- 文摘
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类维生素a,包括all-trans-retinoic酸(RA)和它的立体异构体9-cis-RA扮演重要角色在调节基因表达,通过与核受体相互作用,在胚胎发育和成年的维护上皮组织(Chambon, p (1995) Rec,掠夺。霍恩。> 317 - 32;Mangelsdorf,积累d J。埃文斯,r . m . 83(1995)细胞,841 - 850;Petkovich, m(1992)为基础。启减轻。12日,443 - 471)。证据表明,4-hydroxylation靶细胞内的RA限制了其生物活性和启动一个趋向下降的RA的过程导致其最终消除。然而,18-hydroxylation glucuronidation也可能在这一过程中重要的步骤。在这篇文章中,我们描述第一个哺乳动物的克隆和表征视黄acid-inducible视黄acid-metabolizing细胞色素P450 (hP450RAI),属于小说类的细胞色素(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.