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Sci. STKE, 20 March 2001
Vol. 2001, Issue 74, p. tw2
[DOI: 10.1126/stke.2001.74.tw2]

EDITORS' CHOICE

Transcription Methylation Regulates STAT

Cytokine receptors like the interferon (IFN) receptor cause activation of STAT (signal transducers and activators of transcription) transcription factors. STAT proteins are regulated by phosphorylation on tyrosine and serine phosphorylation. Mowen et al. now show that STAT1 is also posttranslationally modified by methylation on a highly conserved arginine residue. Protein arginine methyl-transferase PRMT1 associates with the interferon-α/β receptor in yeast two-hybrid screen and inhibition of PRMT1 expression with antisense oligonucleotides decreases the effects of type I interferons. Mowen et al. show that STAT1 can be methylated in vitro. Furthermore, methylation of STAT1 (detected with antibodies to dimethylarginine) was increased in mammalian cell lines treated with IFN-α and the methylation was blocked by 5'-methyl-thioadenosine (MTA), a protein methyltransferase inhibitor. MTA also inhibited interferon-induced gene expression. The authors also observed that treatment of cells with MTA reduced DNA-binding activity of STAT1, an effect that correlated with increased association of STAT1 with PIAS1 (the protein inhibitor of activated STATs). MTA is a metabolic intermediate that is a substrate for methyl-thioadenosine phospohorylase (MTAP), and the MTAP gene is deleted in some human cancer cells. Mowen et al. show that accumulation of MTA in cells lacking MTAP can inhibit methylation of STAT1 and appears to make such cells resistant to the effects of interferon.

K. A. Mowen, J. Tang, W. Zhu, B. T. Schurter, K. Shuai, H. R. Herschman, M. David, Arginine methylation of STAT1 modulates IFNα/β-induced transcription. Cell 104, 731-741 (2001). [Online Journal]

Citation: Methylation Regulates STAT. Sci. STKE 2001, tw2 (2001).


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