کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
8457031 1548791 2017 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
SHARPIN Facilitates p53 Degradation in Breast Cancer Cells
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی تحقیقات سرطان
پیش نمایش صفحه اول مقاله
SHARPIN Facilitates p53 Degradation in Breast Cancer Cells
چکیده انگلیسی
The ubiquitin binding protein SHAPRIN is highly expressed in human breast cancer, one of the most frequent female malignancies worldwide. Here, we perform SHARPIN depletion in breast cancer cells together with RNA sequencing. The global expression profiling showed p53 signaling as a potential SHARPIN target. SHARPIN depletion decreased cell proliferation, which effect could be rescue by p53 knocking down. Depletion SHARPIN significantly increases p53 protein level and its target genes in multiple breast cancer cell lines. Further experiment revealed that SHARPIN could facilitate p53 poly-ubiquitination and degradation in MDM2 dependent manner. Immuno-precipitation assay showed that SHARPIN associated with MDM2 and prolonged MDM2 protein stability. Analysis of public available database showed SHARPIN correlated with poor prognosis specifically in p53 wild-type breast cancer patients. Together, our finding revealed a novel modifier for p53/MDM2 complex and suggested SHARPIN as a promising target to restore p53 function in breast cancer.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neoplasia - Volume 19, Issue 2, February 2017, Pages 84-92
نویسندگان
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