Wenqi XU will defend her PhD thesis in life and health sciences, under the supervision of Mohammed BENDAHMANE (ENS de Lyon) and Jun YAN (East China Normal University), on June 12, 2025 at 9:30 am.

Thesis abstract

The growth and development of plants and animals are regulated by signaling pathways, some of which are specific to each kingdom, while others are common to both. One key pathway, shared by plants and animals, controls cell proliferation and organ growth by regulating  cell cycle progression and cell division, with the TRANSLATIONALLY CONTROLLED TUMOR PROTEIN (TCTP) as its main regulator. TCTP is implicated in many cellular processes but its exact function remains difficult to study due to the lethality of the knockout in all eukaryotes. Our team overcame this difficulty by developing a mutant model in Arabidopsis, the first eukaryotic organism with a complete knockout of TCTP, which allows the study of TCTP’s role in plant development.

We have shown that TCTP specifically regulates the G1/S transition of the cell cycle and interacts with CSN4, a subunit of the CONSTITUTIVE PHOTOMORPHOGENESIS 9 (COP9) signalosome, a protein complex essential for several cellular processes, including cell proliferation and hormonal signaling. TCTP/CSN4 interaction, by modulating COP9 activity, controls the progression of the cell cycle by modulating the neddylation of CULLIN subunit and thus the activity of CRLs, a major class of ubiquitin ligases, both in plants and animals. However, the downstream targets of this pathway remain unknown.

In the first part of her PhD thesis, Wenqi Xu used a targeted approach to investigate the implication of known regulators of cell cycle progression, especially during the G1/S transition, downstream of TCTP. Among these genes, she specifically focused on the KRPs, E2Fs, and RBR.

She demonstrated that the mutation of KRPs could not complement the lethal phenotype of the tctp-/- mutants. On the contrary, the accumulation level of KRPs was already decreased in the roots of the tctp-/- mutants. In addition, the study of the accumulation of E2Fa/b/c and RBR showed no changes in the accumulation of E2Fa and RBR, but the accumulation of E2Fb and E2Fc proteins was reduced in the tctp-/- mutants. These results suggest that the canonical inhibitors of the cell cycle, KRPs and E2Fc, are not the targets of the TCTP pathway. These data also suggest a potential feedback mechanism to compensate for the slower cell cycle progression in these mutants by the decrease of these cell cycle inhibitors. Wenqi Xu's data indicate that the TCTP protein regulates the G1/S phase of the cell cycle through the regulation of E2Fa/b. However, it is still possible that TCTP regulates the G1/S phase through a pathway independent of the traditional cell cycle regulation pathway.

In a second part of her PhD thesis, she used a non-targeted approach to identify the downstream factors of the TCTP pathway. A proteomic comparison revealed seven proteins whose accumulation varies inversely in the tctp and csn4 mutant lines, three of which are related to the plant's response to gravity. She showed that the mutation of TCTP affects the plant’s gravitropic response and modifies the redistribution of auxin, confirming the role of TCTP in this process. (Xu et al., manuscript under redaction).

In summary, during her PhD thesis, Wenqi Xu made important theoretical and experimental discoveries on the molecular regulatory mechanism of TCTP pathway in plants. Her results provide a new perspective for understanding the effect of TCTP on the cell cycle regulation mechanisms, as well as on plant growth and development. These results open up prospects for a deeper understanding of the regulation of the plant cell cycle and organ growth, and could contribute to a better understanding of the signaling networks involved in their development.