کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1931131 1050542 2011 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Transgenic overexpression of USP15 in the heart induces cardiac remodeling in mice
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Transgenic overexpression of USP15 in the heart induces cardiac remodeling in mice
چکیده انگلیسی

We found a novel protein–protein interaction between ubiquitin-specific protease 15 (USP15) and skeletal muscle LIM protein 1 (SLIM1): USP15 and SLIM1 directly bound under cell-free conditions and co-immunoprecipitated from the lysates of the cells, where they were co-expressed; and USP15 deubiquitinated SLIM1, resulting in the increase of protein levels of SLIM1. Because SLIM1 is strongly implicated in the pathogenesis of myopathies and cardiomyopathies, we generated transgenic (TG) mice with cardiac-specific overexpression of human USP15. Heart weight to body weight ratios and mRNA levels of fetal gene markers in the heart were significantly higher in USP15-TG mice than in wild-type (WT) mice. Also, protein levels of endogenous murine SLIM1 in the heart were significantly higher in USP15-TG mice than in WT mice. Furthermore, the protein of alternatively spliced isoform of SLIM1 was only detected in the heart of USP15-TG mice, and mRNA levels of this isoform were higher as compared to WT mice. These results indicate that USP15 is involved in the regulation of hypertrophic responses in cardiac muscle through transcriptional and post-translational modulation of SLIM1.

Research highlights
► USP15 directly interacts with SLIM1, and deubiquitinates and stabilizes SLIM1.
► USP15 overexpression in transgenic mice induces cardiac hypertrophic responses.
► Protein levels of SLIM1 increases in the heart of USP15-trangenic (TG) mice.
► Splice variant isoform of SLIM1 is upregulated at mRNA and protein levels in TG mice.
► USP15 induces cardiac hypertrophic responses partly by upregulating SLIM1.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical and Biophysical Research Communications - Volume 405, Issue 2, 11 February 2011, Pages 216–221
نویسندگان
, , , , , , , , ,