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https://hdl.handle.net/2440/104564
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dc.contributor.author | Li, N. | - |
dc.contributor.author | Fassl, A. | - |
dc.contributor.author | Chick, J. | - |
dc.contributor.author | Inuzuka, H. | - |
dc.contributor.author | Li, X. | - |
dc.contributor.author | Mansour, M. | - |
dc.contributor.author | Liu, L. | - |
dc.contributor.author | Wang, H. | - |
dc.contributor.author | King, B. | - |
dc.contributor.author | Shaik, S. | - |
dc.contributor.author | Gutierrez, A. | - |
dc.contributor.author | Ordureau, A. | - |
dc.contributor.author | Otto, T. | - |
dc.contributor.author | Kreslavsky, T. | - |
dc.contributor.author | Baitsch, L. | - |
dc.contributor.author | Bury, L. | - |
dc.contributor.author | Meyer, C. | - |
dc.contributor.author | Ke, N. | - |
dc.contributor.author | Mulry, K. | - |
dc.contributor.author | Kluk, M. | - |
dc.contributor.author | et al. | - |
dc.date.issued | 2014 | - |
dc.identifier.citation | Nature Cell Biology, 2014; 16(11):1080-+ | - |
dc.identifier.issn | 1465-7392 | - |
dc.identifier.issn | 1476-4679 | - |
dc.identifier.uri | http://hdl.handle.net/2440/104564 | - |
dc.description.abstract | Cyclin C was cloned as a growth-promoting G1 cyclin, and was also shown to regulate gene transcription. Here we report that in vivo cyclin C acts as a haploinsufficient tumour suppressor, by controlling Notch1 oncogene levels. Cyclin C activates an 'orphan' CDK19 kinase, as well as CDK8 and CDK3. These cyclin-C-CDK complexes phosphorylate the Notch1 intracellular domain (ICN1) and promote ICN1 degradation. Genetic ablation of cyclin C blocks ICN1 phosphorylation in vivo, thereby elevating ICN1 levels in cyclin-C-knockout mice. Cyclin C ablation or heterozygosity collaborates with other oncogenic lesions and accelerates development of T-cell acute lymphoblastic leukaemia (T-ALL). Furthermore, the cyclin C encoding gene CCNC is heterozygously deleted in a significant fraction of human T-ALLs, and these tumours express reduced cyclin C levels. We also describe point mutations in human T-ALL that render cyclin-C-CDK unable to phosphorylate ICN1. Hence, tumour cells may develop different strategies to evade inhibition by cyclin C. | - |
dc.description.statementofresponsibility | Na Li, Anne Fassl, Joel Chick, Hiroyuki Inuzuka, Xiaoyu Li, …, Charles G. Mullighan … et al. | - |
dc.language.iso | en | - |
dc.publisher | Nature Publishing Group | - |
dc.rights | © 2014 Macmillan Publishers Limited. All rights reserved. | - |
dc.source.uri | http://dx.doi.org/10.1038/ncb3046 | - |
dc.subject | Cancer; cell division; tumour-suppressor proteins | - |
dc.title | Cyclin C is a haploinsufficient tumour suppressor | - |
dc.type | Journal article | - |
dc.identifier.doi | 10.1038/ncb3046 | - |
pubs.publication-status | Published | - |
dc.identifier.orcid | Mullighan, C. [0000-0002-1871-1850] | - |
Appears in Collections: | Aurora harvest 8 Medicine publications |
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