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DOI | 10.1038/s41467-019-08306-x |
MYC dephosphorylation by the PP1/PNUTS phosphatase complex regulates chromatin binding and protein stability | |
Dingar, Dharmendra1; Tu, William B.1,2; Resetca, Diana1,2; Lourenco, Corey1,2; Tamachi, Aaliya1; De Melo, Jason1; Houlahan, Kathleen E.2,3; Kalkat, Manpreet1,2; Chan, Pak-Kei1; Boutros, Paul C.2,3,4; Raught, Brian1,2; Penn, Linda Z.1,2 | |
2019-01-29 | |
发表期刊 | NATURE COMMUNICATIONS
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ISSN | 2041-1723 |
出版年 | 2018 |
卷号 | 9 |
文章类型 | Article |
语种 | 英语 |
国家 | Canada |
英文摘要 | The c-MYC (MYC) oncoprotein is deregulated in over 50% of cancers, yet regulatory mechanisms controlling MYC remain unclear. To this end, we interrogated the MYC inter-actome using BioID mass spectrometry (MS) and identified PP1 (protein phosphatase 1) and its regulatory subunit PNUTS (protein phosphatase-1 nuclear-targeting subunit) as MYC interactors. We demonstrate that endogenous MYC and PNUTS interact across multiple cell types and that they co-occupy MYC target gene promoters. Inhibiting PP1 by RNAi or pharmacological inhibition results in MYC hyperphosphorylation at multiple serine and threonine residues, leading to a decrease in MYC protein levels due to proteasomal degradation through the canonical SCFFBXW7 pathway. MYC hyperphosphorylation can be rescued specifically with exogenous PP1, but not other phosphatases. Hyperphosphorylated MYC retained interaction with its transcriptional partner MAX, but binding to chromatin is significantly compromised. Our work demonstrates that PP1/PNUTS stabilizes chromatin-bound MYC in proliferating cells. |
领域 | 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000442998800007 |
WOS关键词 | C-MYC ; CANCER ; PHOSPHORYLATION ; TRANSCRIPTION ; ONCOPROTEIN ; SOFTWARE ; TARGET ; CELLS ; TRANSFORMATION ; TUMORIGENESIS |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
URL | 查看原文 |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/204191 |
专题 | 资源环境科学 |
作者单位 | 1.Univ Hlth Network, Princess Margaret Canc Ctr, Toronto, ON M5G 1L7, Canada; 2.Univ Toronto, Dept Med Biophys, Toronto, ON M5G 1L7, Canada; 3.Ontario Inst Canc Res, Toronto, ON M5G 0A3, Canada; 4.Univ Toronto, Dept Pharmacol & Toxicol, Toronto, ON M5S 1A8, Canada |
推荐引用方式 GB/T 7714 | Dingar, Dharmendra,Tu, William B.,Resetca, Diana,et al. MYC dephosphorylation by the PP1/PNUTS phosphatase complex regulates chromatin binding and protein stability[J]. NATURE COMMUNICATIONS,2019,9. |
APA | Dingar, Dharmendra.,Tu, William B..,Resetca, Diana.,Lourenco, Corey.,Tamachi, Aaliya.,...&Penn, Linda Z..(2019).MYC dephosphorylation by the PP1/PNUTS phosphatase complex regulates chromatin binding and protein stability.NATURE COMMUNICATIONS,9. |
MLA | Dingar, Dharmendra,et al."MYC dephosphorylation by the PP1/PNUTS phosphatase complex regulates chromatin binding and protein stability".NATURE COMMUNICATIONS 9(2019). |
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