期刊
EMBO JOURNAL
卷 37, 期 20, 页码 -出版社
WILEY
DOI: 10.15252/embj.201899395
关键词
BCL9; BCL9 phosphorylation; CDK1; cell division; clathrin; mitosis; spindle; Wnt signalling
资金
- National Medical Research Council of Singapore [NRNMRMH16101]
- Key projects of National Natural Science Foundation of China [81730108]
- Key Project of Zhejiang province Ministry of Science and Technology [2015C03055]
- Key Project of Hangzhou Ministry of Science and Technology [20162013A07, 20142013A63]
- SingHealth Foundation
- Start-up Grant of HZNU
- National Natural Science Foundation of China [81802338]
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 BCL9N-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.
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