کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1931270 1050547 2011 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
TLS and PRMT1 synergistically coactivate transcription at the survivin promoter through TLS arginine methylation
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
TLS and PRMT1 synergistically coactivate transcription at the survivin promoter through TLS arginine methylation
چکیده انگلیسی

TLS (Translocated in LipoSarcoma), also termed FUS, is a multifunctional protein implicated in diverse cellular events such as maintaining genome integrity and regulating gene expression. We have focused on the role of TLS as a coregulator in transcriptional regulation. In the process of investigating TLS-binding proteins, we found that PRMT1 (protein arginine methyltransferase 1) was in complex with TLS. We analyzed the methylation status of endogenous TLS and demonstrated that TLS was arginine-methylated by PRMT1. Using mass spectrometry, we identified that four arginine residues within TLS (R216, R218, R242 and R394) were consistently dimethylated. We performed luciferase reporter assays to assess the functional consequence of TLS arginine methylation in transcriptional regulation and, interestingly, observed that TLS and PRMT1 synergistically coactivated transcription at the survivin promoter. Further analysis using a catalytic-dead PRMT1 or methylation inhibitor both showed that the synergistic transcriptional activation was mediated by TLS arginine-methylation. These results revealed a cooperative role of TLS and PRMT1 in transcriptional regulation.

Research highlights
► TLS/FUS is associated with and arginine-methylated by PRMT1.
► Four arginine residues within TLS (R216, R218, R242 and R394) are consistently dimethylated.
► TLS and PRMT1 synergistically coactivate transcription at the survivin promoter.
► Both the enzymatic activity of PRMT1 and arginine methylation of TLS are required for synergistic transcriptional activation at survivin promoter.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical and Biophysical Research Communications - Volume 404, Issue 4, 28 January 2011, Pages 991–996
نویسندگان
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