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

Jianxiang Chen; Muthukumar Rajasekaran; Hongping Xia; Shik Nie Kong; Amudha Deivasigamani; Karthik Sekar; Hengjun Gao; Hannah L.F. Swa; Jayantha Gunaratne; London Lucien Ooi; Tian Xie; Wanjin Hong; Kam Man Hui

doi:10.15252/embj.201899395

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

Jianxiang Chen
, Muthukumar Rajasekaran
, Hongping Xia
, Shik Nie Kong
, Amudha Deivasigamani
, Karthik Sekar
, Hengjun Gao
, Hannah L.F. Swa
, Jayantha Gunaratne
, London Lucien Ooi
, Tian Xie
, Wanjin Hong
, Kam Man Hui

Health Science Center

Research output: Contribution to journal › Article › peer-review

25 Scopus citations

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.

Original language	English
Article number	e99395
Journal	EMBO Journal
Volume	37
Issue number	20
DOIs	https://doi.org/10.15252/embj.201899395
State	Published - 15 Oct 2018

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

BCL9
BCL9 phosphorylation
CDK1
cell division
clathrin
mitosis
spindle
Wnt signalling

Access to Document

10.15252/embj.201899395

Cite this

@article{d2a83d40c3ef461282f7c686999cb786,

title = "CDK1-mediated BCL9 phosphorylation inhibits clathrin to promote mitotic Wnt signalling",

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.",

keywords = "BCL9, BCL9 phosphorylation, CDK1, cell division, clathrin, mitosis, spindle, Wnt signalling",

author = "Jianxiang Chen and Muthukumar Rajasekaran and Hongping Xia and Kong, \{Shik Nie\} and Amudha Deivasigamani and Karthik Sekar and Hengjun Gao and Swa, \{Hannah L.F.\} and Jayantha Gunaratne and Ooi, \{London Lucien\} and Tian Xie and Wanjin Hong and Hui, \{Kam Man\}",

note = "Publisher Copyright: {\textcopyright} 2018 The Authors",

year = "2018",

month = oct,

day = "15",

doi = "10.15252/embj.201899395",

language = "英语",

volume = "37",

journal = "EMBO Journal",

issn = "0261-4189",

publisher = "Springer Science and Business Media Deutschland GmbH",

number = "20",

}

TY - JOUR

T1 - CDK1-mediated BCL9 phosphorylation inhibits clathrin to promote mitotic Wnt signalling

AU - Chen, Jianxiang

AU - Rajasekaran, Muthukumar

AU - Xia, Hongping

AU - Kong, Shik Nie

AU - Deivasigamani, Amudha

AU - Sekar, Karthik

AU - Gao, Hengjun

AU - Swa, Hannah L.F.

AU - Gunaratne, Jayantha

AU - Ooi, London Lucien

AU - Xie, Tian

AU - Hong, Wanjin

AU - Hui, Kam Man

PY - 2018/10/15

Y1 - 2018/10/15

N2 - 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.

AB - 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.

KW - BCL9

KW - BCL9 phosphorylation

KW - CDK1

KW - cell division

KW - clathrin

KW - mitosis

KW - spindle

KW - Wnt signalling

UR - https://www.scopus.com/pages/publications/85053473493

U2 - 10.15252/embj.201899395

DO - 10.15252/embj.201899395

M3 - 文章

C2 - 30217955

AN - SCOPUS:85053473493

SN - 0261-4189

VL - 37

JO - EMBO Journal

JF - EMBO Journal

IS - 20

M1 - e99395

ER -

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

Abstract

UN SDGs

Keywords

Access to Document

Other files and links

Fingerprint

Cite this