| Literature DB >> 30217955 |
Jianxiang Chen1,2,3, Muthukumar Rajasekaran2, Hongping Xia2, Shik Nie Kong2, Amudha Deivasigamani2, Karthik Sekar2, Hengjun Gao2, Hannah Lf Swa3, Jayantha Gunaratne3, London Lucien Ooi4, Tian Xie5, Wanjin Hong3, Kam Man Hui1,2,3,6,7.
Abstract
Uncontrolled cell division is a hallmark of cancer. Deregulation of Wnt components has been linked to aberrant cell division by multiple mechanisms, including Wnt-mediated stabilisation of proteins signalling, which was notably observed in mitosis. Analysis of Wnt components revealed an unexpected role of B-cell CLL/lymphoma 9 (BCL9) in maintaining mitotic Wnt signalling to promote precise cell division and growth of cancer cell. Mitotic interactome analysis revealed a mechanistic role of BCL9 in inhibiting clathrin-mediated degradation of LRP6 signalosome components by interacting with clathrin and the components in Wnt destruction complex; this function was further controlled by CDK1-driven phosphorylation of BCL9 N-terminal, especially T172. Interestingly, T172 phosphorylation was correlated with cancer patient prognosis and enriched in tumours. Thus, our results revealed a novel role of BCL9 in controlling mitotic Wnt signalling to promote cell division and growth.Entities:
Keywords: BCL9; BCL9 phosphorylation; CDK1; Wnt signalling; cell division; clathrin; mitosis; spindle
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Year: 2018 PMID： 30217955 PMCID： PMC6187222 DOI： 10.15252/embj.201899395
Source DB: PubMed Journal: EMBO J ISSN： 0261-4189 Impact factor: 11.598