Alternative Splicing Yields Protein Arginine Methyltransferase 1 Isoforms with Distinct Activity, Substrate Specificity, and Subcellular Localization

Goulet, Isabelle; Gauvin, Gabrielle; Boisvenue, Sophie; Côté, Jocelyn

doi:10.1074/jbc.m704349200

Cited by 161 publications

(217 citation statements)

References 76 publications

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“…It has been reported that alternative splicing of the human PRMT1 primary transcript can give rise to at least three protein isoforms, and that their N-termini are different from one another. 44) Goulet et al 52) have further extended these findings, and have confirmed that the complex genomic organization of the 5 0 -end of the PRMT1 gene can produce up to seven protein isoforms, with molecular masses of 40.5, 42.5, 39.8, 40.1, 39.4, 37.7, and 36.7 kDa, designated v1-7 respectively, expressed in a tissue-specific manner. Our findings provide the first evidence that PRMT1 isoforms are expressed in a tissue-specific manner in the rat as well as the mouse and humans.…”

Section: Discussionsupporting

confidence: 50%

Asymmetric Dimethylarginine, an Endogenous NOS Inhibitor, Is Actively Metabolized in Rat Erythrocytes

Yokoro¹,

Suzuki²,

Murota³

et al. 2012

Bioscience, Biotechnology, and Biochemistry

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Section: Discussionsupporting

confidence: 50%

Asymmetric Dimethylarginine, an Endogenous NOS Inhibitor, Is Actively Metabolized in Rat Erythrocytes

Yokoro¹,

Suzuki²,

Murota³

et al. 2012

Bioscience, Biotechnology, and Biochemistry

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“…As shown in Figure 2a, only wild-type (WT) GST-PRMT1 methylated the N-terminus of Axin, compared with dominantnegative GST-PRMT1 which has no enzymatic activity (McBride et al, 2000). PRMT1 is a type I arginine methyltransferase, a group that includes PRMT3, PRMT4/Carm1 and PRMT6 (Bedford and Clarke, 2009), and has several splicing variants (Goulet et al, 2007). Among them, PRMT1, PRMT3 and PRMT6 methylate substrates have a conserved glycine/argininerich (GAR) motif, whereas PRMT4/Carm1 has different motif (Boisvert et al, 2005).…”

Section: Resultsmentioning

confidence: 99%

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

Cha

Kim

et al. 2011

Oncogene

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Axin, a negative regulator of Wnt signaling, is a key scaffold protein for the b-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 3b, 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 b-catenin as well as b-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/b-catenin signaling.

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“…The loss of PRMT1 increased the levels of MMA and SDMA, and PRMT1 is transported between the nucleus and cytoplasm depending on the methylation status of substrate proteins in several cells [21]. On the other hand, PRTM1 has some splicing variants, and the noncoding variant of PRMT1, PRMT1 variant 2, was reported to be associated with progression of both colon and breast cancer [13,22]. Moreover, it was reported that PRMT1 functions such as substrate recognition and methylation are inhibited by phosphorylation of Tyr291 [23].…”

Section: Discussionmentioning

confidence: 99%

Nuclear PRMT1 expression is associated with poor prognosis and chemosensitivity in gastric cancer patients

et al. 2015

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Background Metastatic and refractory gastric cancer (GC) are associated with a poor prognosis; therefore, the identification of prognostic factors and chemosensitivity markers is extremely important. Protein arginine methyltransferase 1 (PRMT1) may play a role in chemosensitivity/apoptosis induction via activation of the tumor suppressor forkhead box O1 (FOXO1). The purpose of this study was to clarify the expression of and relationship between PRMT1 and FOXO1 to evaluate the applicability of PRMT1 as a prognostic marker and a therapeutic tool in GC. Methods We investigated the clinical and functional significance of PRMT1 and FOXO1 in 195 clinical GC samples using immunohistochemistry. We performed suppression analysis of PRMT1 using small interfering RNA to determine the biological roles of PRMT1 in chemosensitivity. Results PRMT1 and FOXO1 in GC samples were predominantly expressed in the nucleus. Patients with lower PRMT1 expression (n = 131) had suppressed nuclear accumulation of FOXO1, higher recurrence after adjuvant chemotherapy, and poorer prognosis than those with higher PRMT1 expression (n = 64). PRMT1 downregulation in GC cells by RNA interference inhibited cisplatin and 5-fluorouracil sensitivity. The expression of phosphorylated FOXO1 and phosphorylated BCL-2 antagonist of cell death was upregulated in PRMT1 small interfering RNA groups. Conclusion Our data suggest that the evaluation of PRMT1 expression in GC is a useful predictor of poor prognosis and recurrence after adjuvant chemotherapy. Moreover, these data suggest that PRMT1 is a promising therapeutic tool for overcoming refractory GC.

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Alternative Splicing Yields Protein Arginine Methyltransferase 1 Isoforms with Distinct Activity, Substrate Specificity, and Subcellular Localization

Cited by 161 publications

References 76 publications

Asymmetric Dimethylarginine, an Endogenous NOS Inhibitor, Is Actively Metabolized in Rat Erythrocytes

Asymmetric Dimethylarginine, an Endogenous NOS Inhibitor, Is Actively Metabolized in Rat Erythrocytes

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

Nuclear PRMT1 expression is associated with poor prognosis and chemosensitivity in gastric cancer patients

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