CDK1-mediated BCL9 phosphorylation inhibits clathrin to promote mitotic Wnt signalling

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.

Source: EMBO Journal - October 15, 2018 Category: Molecular Biology Authors: Chen, J., Rajasekaran, M., Xia, H., Kong, S. N., Deivasigamani, A., Sekar, K., Gao, H., Swa, H. L., Gunaratne, J., Ooi, L. L., Xie, T., Hong, W., Hui, K. M. Tags: Cancer, Cell Cycle, Signal Transduction Articles Source Type: research