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

B. Cha, W. Kim, Y. K. Kim, B. N. Hwang, S. Y. Park, J. W. Yoon, W. S. Park, J. W. Cho, M. T. Bedford, E. H. Jho

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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.

Original languageEnglish
Pages (from-to)2379-2389
Number of pages11
JournalOncogene
Volume30
Issue number20
DOIs
Publication statusPublished - 2011 May 19

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Cancer Research

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    Cha, B., Kim, W., Kim, Y. K., Hwang, B. N., Park, S. Y., Yoon, J. W., Park, W. S., Cho, J. W., Bedford, M. T., & Jho, E. H. (2011). Methylation by protein arginine methyltransferase 1 increases stability of Axin, a negative regulator of Wnt signaling. Oncogene, 30(20), 2379-2389. https://doi.org/10.1038/onc.2010.610