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Differential use of an in-frame translation initiation codon regulates human mu opioid receptor (OPRM1)

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Abstract

The pharmacological effects of morphine and morphine-like drugs are mediated primarily through the µ opioid receptor. Here we show that differential use of an in-frame translational start codon in the 5′-untranslated region of the OPRM1 generates different translational products in vivo and in vitro. The 5′-end of the OPRM1 gene is necessary for initiating the alternate form and for subsequent degradation of the protein. Initiation of OPRM1 at the upstream site decreases the initiation at the main AUG site. However, alternative initiation of the long form of OPRM1 produces a protein with a short half-life, resulting from degradation mediated by the ubiquitin–proteasome pathway. Reporter and degradation assays showed that mutations of this long form at the second and third lysines reduce ubiquitin-dependent proteasome degradation, stabilizing the protein. The data suggest that MOP expression is controlled in part by initiation of the long form of MOP at the alternate site.

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Acknowledgments

This work was supported by National Institutes of Health research grants DA000564, DA001583, DA011806, K05-DA070554, DA011190, and DA013926, and by the A&F Stark Fund of the Minnesota Medical Foundation.

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Author notes

  1. Chun Sung Kim

    Present address: Department of Oral Physiology, Chosun University, Gwangju, South Korea

Authors and Affiliations

  1. Department of Pharmacology, University of Minnesota Medical School, Minneapolis, MN, 55455, USA

    Kyu Young Song, Hack Sun Choi, Cheol Kyu Hwang, Ping-Yee Law, Li-Na Wei & Horace H. Loh

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  1. Kyu Young Song
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Correspondence to Kyu Young Song.

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Song, K.Y., Choi, H.S., Hwang, C.K. et al. Differential use of an in-frame translation initiation codon regulates human mu opioid receptor (OPRM1). Cell. Mol. Life Sci. 66, 2933–2942 (2009). https://doi.org/10.1007/s00018-009-0082-7

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