Academic Journal
VprBP directs epigenetic gene silencing through histone H2A phosphorylation in colon cancer
| العنوان: | VprBP directs epigenetic gene silencing through histone H2A phosphorylation in colon cancer |
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| المؤلفون: | Ghate, Nikhil Baban, Kim, Sangnam, Spiller, Erin, Kim, Sungmin, Shin, Yonghwan, Rhie, Suhn K., Smbatyan, Goar, Lenz, Heinz‐Josef, Mumenthaler, Shannon M., An, Woojin |
| المساهمون: | National Institutes of Health, National Cancer Institute |
| المصدر: | Molecular Oncology ; volume 15, issue 10, page 2801-2817 ; ISSN 1574-7891 1878-0261 |
| بيانات النشر: | Wiley |
| سنة النشر: | 2021 |
| المجموعة: | Wiley Online Library (Open Access Articles via Crossref) |
| الوصف: | Histone modification is aberrantly regulated in cancer and generates an unbalanced state of gene transcription. VprBP, a recently identified kinase, phosphorylates histone H2A on threonine 120 (T120) and is involved in oncogenic transcriptional dysregulation; however, its specific role in colon cancer is undefined. Here, we show that VprBP is overexpressed in colon cancer and directly contributes to epigenetic gene silencing and cancer pathogenesis. Mechanistically, the observed function of VprBP is mediated through H2AT120 phosphorylation (H2AT120p)‐driven transcriptional repression of growth regulatory genes, resulting in a significantly higher proliferative capacity of colon cancer cells. Our preclinical studies using organoid and xenograft models demonstrate that treatment with the VprBP inhibitor B32B3 impairs colonic tumor growth by blocking H2AT120p and reactivating a transcriptional program resembling that of normal cells. Collectively, our work describes VprBP as a master kinase contributing to the development and progression of colon cancer, making it a new molecular target for novel therapeutic strategies. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1002/1878-0261.13068 |
| الاتاحة: | http://dx.doi.org/10.1002/1878-0261.13068 https://onlinelibrary.wiley.com/doi/pdf/10.1002/1878-0261.13068 https://onlinelibrary.wiley.com/doi/full-xml/10.1002/1878-0261.13068 https://febs.onlinelibrary.wiley.com/doi/pdf/10.1002/1878-0261.13068 |
| Rights: | http://creativecommons.org/licenses/by/4.0/ |
| رقم الانضمام: | edsbas.1020D3C0 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1002/1878-0261.13068 |
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