TCTP and CSN4 control cell cycle progression and development by regulating CULLIN1 neddylation in plants and animals

Translationally Controlled Tumor Protein (TCTP) controls growth by regulating the G1/S transition during cell cycle progression. Our genetic interaction studies show that TCTP fulfills this role by interacting with CSN4, a subunit of the COP9 Signalosome complex, known to influence CULLIN-RING ubiquitin ligases activity by controlling CULLIN (CUL) neddylation status. In agreement with these data, downregulation of CSN4 in Arabidopsis and in tobacco cells leads to delayed G1/S transition comparable to that observed when TCTP is downregulated. Loss-of-function of AtTCTP leads to increased fraction of deneddylated CUL1, suggesting that AtTCTP interferes negatively with COP9 function. Similar defects in cell proliferation and CUL1 neddylation status were observed in Drosophila knockdown for dCSN4 or dTCTP, respectively, demonstrating a conserved mechanism between plants and animals. Together, our data show that CSN4 is the missing factor linking TCTP to the control of cell cycle progression and cell proliferation during organ development and open perspectives towards understanding TCTP’s role in organ development and disorders associated with TCTP miss-expression.

Citation

Léo Betsch, Véronique Boltz, Florian Brioudes, Garance Pontier, Victor Girard, Julie Savarin, Barbara Wipperman, Pierre Chambrier, Nicolas Tissot, Moussa Benhamed, Bertrand Mollereau, Cécile Raynaud, Mohammed Bendahmane, Judit Szécsi, Jian Hua. TCTP and CSN4 control cell cycle progression and development by regulating CULLIN1 neddylation in plants and animals PLoS Genetics. 2019 Jan 29;15(1)

PMID: 30695029

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