Cytochrome P450 1B1 mRNA untranslated regions interact to inhibit protein translation.

Abstract	CYP1B1 mRNA is expressed constitutively in all normal extrahepatic human tissues, though the protein is usually undetectable. In contrast, CYP1B1 protein is expressed at high levels in tumors. In this study CYP1B1 mRNA and protein expression was measured in a panel of cell lines indicating that CYP1B1 regulation is altered in tumor cell lines in vitro. Interrogation of ONCOMINE revealed that CYP1B1 mRNA is not significantly overexpressed in tumors compared to normal tissues, suggesting CYP1B1 is subject to posttranscriptional control. Analysis of the CYP1B1 mRNA revealed a complex 5' untranslated region (UTR) containing a small upstream open-reading frame (uORF). These features are present in mRNAs subject to translational control so the effect of the 5'UTR was tested using in vitro translation in CHO-K1 cells. The 5'UTR significantly inhibited luciferase reporter gene translation, and mutation of the uORF start codon abolished the inhibitory effect. The 5'UTR also interacted with the microRNA-27b recognition element in the CYP1B1 mRNA 3'UTR to almost completely inhibit translation. CYP1B1 is subject to a high degree of translational control, which may explain the absence of protein expression in normal cells. Alterations in translational control during malignant transformation may help to explain the tumor-specific expression of CYP1B1 protein.
Authors	Andrea H Devlin, Paul Thompson, Tracy Robson, Stephanie R McKeown
Journal	Molecular carcinogenesis (Mol Carcinog) Vol. 49 Issue 2 Pg. 190-9 (Feb 2010) ISSN: 1098-2744 [Electronic] United States
PMID	19908239 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	5' Untranslated Regions DNA Primers Proteins RNA, Messenger Cytochrome P-450 Enzyme System Aryl Hydrocarbon Hydroxylases CYP1B1 protein, human Cytochrome P-450 CYP1B1
Topics	5' Untranslated Regions Animals Aryl Hydrocarbon Hydroxylases Base Sequence Blotting, Western CHO Cells Cell Line, Tumor Cricetinae Cricetulus Cytochrome P-450 CYP1B1 Cytochrome P-450 Enzyme System (genetics) DNA Primers Humans Open Reading Frames Polymerase Chain Reaction Protein Biosynthesis Proteins (metabolism) RNA, Messenger (genetics) Sequence Homology, Nucleic Acid

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.

Realize the full power of the drug-disease research graph!