Cell cycle regulation in plants and animals through TCTP/CSN4 complexes

The control of cell proliferation is a key process for proper development in all multicellular organisms. The TCTP protein (Translationally Controlled Tumor Protein), that was first identified for its high abundance in cancer cells is a positive regulator of cell cycle progression. Reciprocal complementation assays had revealed that this protein’s function is conserved between Drosophila and Arabidopsis, but the underlying mechanism remained unknown. The group of M. Bendahmane (RDP, Lyon) has identified the CSN4 protein, a sub-unit of the COP9 signalosome, as an interactor of TCTP. Together with them, we have shown that down-regulation of either CSN4 or TCTP leads to the same delay in cell cycle progression (Figure 1), that corresponds to a prolonged G1 phase. Thanks to the group of B. Mollereaux (LBMC, Lyon), we showed that this mechanism is conserved in Drosophila. Because the COP9 signalosome controls protein ubiquitination through cullin neddylation, we suggest that TCTP/CSN4 complexes control the accumulation of cell cycle regulators, and thereby cell cycle length. Identifying the core cell cycle regulators targeted by this pathway will be the next step to fully understand this regulatory mechanism.

Betsch et al (2018) TCTP and CSN4 control cell cycle progression and development by regulating CULLIN1 neddylation in plants and animals.PLoS Genet. 2019 Jan 29;15(1):e1007899. doi: 10.1371/journal.pgen.1007899.

Figure 1 : Downregulation of CSN4 and TCTP results in similar cell cycle progression defects.

This images shows EdU incorporation in root tips of wild-type plants (WT, left), CSN4 kock-down (CSN4 RNAi, middle) and TCTP knock-down plants (TCTP RNAi, right). EdU is a thymidine analog that incorporates into DNA during replication, and can be revealed with green fluorescence. The lower proportion of EdU positive nuclei (green) in TCTP and CSN4 RNAi lines among total nuclei (labelled with Hoechst in white) after 4h incubation with EdU reveals the cell cycle delay in TCTP RNAi and CSN4 RNAi lines.