Methylation by protein arginine methyltransferase 1 increases stability of Axin, a negative regulator of Wnt signaling.
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.
Department of Life Science, The University of Seoul, Dongdaemun-gu, Seoul, Republic of Korea.
B
B
Cha
W
W
Kim
Y K
YK
Kim
B N
BN
Hwang
S Y
SY
Park
J W
JW
Yoon
W S
WS
Park
J W
JW
Cho
M T
MT
Bedford
E-h
EH
Jho
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D060466:Axin Protein; D002460:Cell Line; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D006801:Humans; D066298:In Vitro Techniques; D008745:Methylation; D011484:Protein-Arginine N-Methyltransferases / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism*; D015398:Signal Transduction; D054875:Ubiquitination; D051153:Wnt Proteins / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D060466:Axin Protein; D012097:Repressor Proteins; D051153:Wnt Proteins; D051176:beta Catenin; D011484:Protein-Arginine N-Methyltransferases