IRIC - Institute for Research in Immunology and Cancer

Published on May 17, 2023

Despite potential roles in the tumorigenesis of lung and breast cancer cells, the atypical protein kinase ERK3, a member of the Ras/MAPK pathway, is poorly characterized. The laboratory of Professor Sylvain Meloche, Director of the Signalling and Cell Growth Research Unit, collaborated with the laboratory of Professor Jean-Claude Labbé, Director of the Cell Division and Differentiation Research Unit, both at IRIC, to identify ERK3 targets and better understand its cellular functions. The work carried out led to the identification of supervillin as a target of ERK3. Published in the Journal of Cellular Physiology, the study was jointly led by postdoctoral fellow Joaquim Javary and research advisor Eugénie Goupil, with the collaboration of research advisor Mathilde Soulez.

A rare confirmed target for ERK3

Phosphoproteomics experiments, which measure levels of protein phosphorylation, in breast cancer cells have identified supervillin as a potential target of ERK3 kinase. Biochemistry experiments subsequently verified that supervilline and ERK3 interact by forming stable complexes. The team also showed that ERK3 phosphorylates supervillin in vitro, suggesting that it is indeed a direct target of the kinase.

An important mechanism for the end of cell division

The researchers then wanted to understand the functional relevance of the phosphorylation of supervillin by ERK3. Through immunofluorescence experiments, the team observed that the ERK3-dependent phosphorylation of supervillin is required for the completion of the last step of cell division, cytokinesis (the physical separation of the two daughter cells). Disruption of the mechanism results in the production of multinucleated cells, which affects cell ploidy (the number of sets of chromosomes they have). Such ploidy disruption can lead to the appearance of abnormal cells, and eventually of tumor cells.

This work provides a better understanding of the oncogenic signaling network of ERK3. Dissecting the roles of ERK3 during cell division is an interesting avenue for the development of new therapeutic strategies.

Cited study :

Joaquim Javary, Eugénie Goupil, Mathilde Soulez, Evgeny Kanshin, Antoine Bouchard, Ole-Morten Seternes, Pierre Thibault, Jean-Claude Labbé, Sylvain Meloche. Phosphoproteomic analysis identifies supervillin as an ERK3substrate regulating cytokinesis and cell ploidy. Journal of Cellular Physiology. 2022; 10.1002/jcp.30938