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Methylation by protein arginine methyltransferase 1 increases stability of Axin, a negative regulator of Wnt signaling

Oncogene volume 30, pages 2379–2389 (2011)Cite this article

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Abstract

Axin, a negative regulator of Wnt signaling, is a key scaffold protein for the β-catenin destruction complex. It has been previously shown that multiple post-translational modification enzymes regulate the level of Axin. Here, we provide evidence that protein arginine methyltransferase 1 (PRMT1) directly interacts with and methylates the 378th arginine residue of Axin both in vitro and in vivo. We found that the transient expression of PRMT1 led to an increased level of Axin and that knockdown of endogenous PRMT1 by short hairpin RNA reduced the level of Axin. These results suggest that methylation by PRMT1 enhanced the stability of Axin. Methylation of Axin by PRMT1 also seemingly enhanced the interaction between Axin and glycogen synthase kinase 3β, leading to decreased ubiquitination of Axin. Consistent with the role of PRMT1 in the regulation of Axin, knockdown of PRMT1 enhanced the level of cytoplasmic β-catenin as well as β-catenin-dependent transcription activity. In summary, we show that the methylation of Axin occurred in vivo and controlled the stability of Axin. Therefore, methylation of Axin by PRMT1 may serve as a finely tuned regulation mechanism for Wnt/β-catenin signaling.

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Acknowledgements

This work was supported by grants from the Korea Research Foundation (C00339) and the National R&D Program for Cancer Control, Ministry for Health and Welfare, Republic of Korea (1020240) to E Jho B Cha, W Kim and B Hwang were supported by the Brain Korea 21 program. B Cha and W Kim were recipients of the Seoul Science Fellowship.

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  1. B Cha and W Kim: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Life Science, The University of Seoul, Seoul, Republic of Korea

    B Cha, W Kim, B N Hwang & E-h Jho

  2. Department of Carcinogenesis, The University of Texas MD Anderson Cancer Center, Smithville, TX, USA

    Y K Kim & M T Bedford

  3. Department of Biology and Department of Integrated OMICS for Biomedical Sciences, World Class University Program, Yonsei University, Seoul, Republic of Korea

    S Y Park & J W Cho

  4. Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea

    J W Yoon & W S Park

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Correspondence to E-h Jho.

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Our work is original research, has not been previously published and has not been submitted for publication elsewhere while under consideration. We declare that there is no competing financial interest in relation to our work described in the manuscript.

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Cha, B., Kim, W., Kim, Y. et al. Methylation by protein arginine methyltransferase 1 increases stability of Axin, a negative regulator of Wnt signaling. Oncogene 30, 2379–2389 (2011). https://doi.org/10.1038/onc.2010.610

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