Ontology highlight
ABSTRACT:
SUBMITTER: Li N
PROVIDER: S-EPMC4235773 | biostudies-literature | 2014 Nov
REPOSITORIES: biostudies-literature
Li Na N Fassl Anne A Chick Joel J Inuzuka Hiroyuki H Li Xiaoyu X Mansour Marc R MR Liu Lijun L Wang Haizhen H King Bryan B Shaik Shavali S Gutierrez Alejandro A Ordureau Alban A Otto Tobias T Kreslavsky Taras T Baitsch Lukas L Bury Leah L Meyer Clifford A CA Ke Nan N Mulry Kristin A KA Kluk Michael J MJ Roy Moni M Kim Sunkyu S Zhang Xiaowu X Geng Yan Y Zagozdzon Agnieszka A Jenkinson Sarah S Gale Rosemary E RE Linch David C DC Zhao Jean J JJ Mullighan Charles G CG Harper J Wade JW Aster Jon C JC Aifantis Iannis I von Boehmer Harald H Gygi Steven P SP Wei Wenyi W Look A Thomas AT Sicinski Piotr P
Nature cell biology 20141026 11
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 l ...[more]