RESUMO
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.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas de Arabidopsis/genética , Complexo do Signalossomo COP9/genética , Proteínas Culina/genética , Proteínas de Drosophila/genética , Proteínas Associadas aos Microtúbulos/genética , Animais , Arabidopsis/genética , Arabidopsis/crescimento & desenvolvimento , Pontos de Checagem do Ciclo Celular/genética , Divisão Celular/genética , Proliferação de Células/genética , Drosophila/genética , Nicotiana/genética , UbiquitinaRESUMO
Phosphate (Pi) starvation response (PHR) transcription factors play key roles in plant Pi homeostasis maintenance. They are negatively regulated by stand-alone SPX proteins, cellular receptors for inositol pyrophosphate (PP-InsP) nutrient messengers. How PP-InsP-bound SPX interacts with PHRs is poorly understood. Here, we report crystal structures of the rice SPX2/InsP6/PHR2 complex and of the PHR2 DNA binding (MYB) domain in complex with target DNA at resolutions of 3.1 Å and 2.7 Å, respectively. In the SPX2/InsP6/PHR2 complex, the signalling-active SPX2 assembles into a domain-swapped dimer conformation and binds two copies of PHR2, targeting both its coiled-coil (CC) oligomerisation domain and MYB domain. Our results reveal that the SPX2 senses PP-InsPs to inactivate PHR2 by establishing severe steric clashes with the PHR2 MYB domain, preventing DNA binding, and by disrupting oligomerisation of the PHR2 CC domain, attenuating promoter binding. Our findings rationalize how PP-InsPs activate SPX receptor proteins to target PHR family transcription factors.
Assuntos
Oryza , Regulação da Expressão Gênica de Plantas , Homeostase , Oryza/genética , Oryza/metabolismo , Fosfatos/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas/metabolismo , Fatores de Transcrição/metabolismoRESUMO
The Translationally Controlled Tumor Protein (TCTP) is a conserved protein which expression was associated with several biochemical and cellular functions. Loss-of-function mutants are lethal both in animals and in plants, making the identification of its exact role difficult. Recent data using the model plant Arabidopsis thaliana provided the first viable adult knockout for TCTP and helped addressing the biological role of TCTP during organ development and the functional conservation between plants and animals. This chapter summarizes our up to date knowledge about the role of TCTP in plants and discuss about conserved functions and mechanisms between plants and animals.