Abstract
14-3-3 family proteins regulate multiple signalling pathways. Understanding biological functions of 14-3-3 proteins has been limited by the functional redundancy of conserved isotypes. Here we provide evidence that 14-3-3 proteins regulate two interacting components of Tor signalling in Drosophila, translationally controlled tumour protein (Tctp) and Rheb GTPase. Single knockdown of 14-3-3ɛ or 14-3-3ζ isoform does not show obvious defects in organ development but causes synergistic genetic interaction with Tctp and Rheb to impair tissue growth. 14-3-3 proteins physically interact with Tctp and Rheb. Knockdown of both 14-3-3 isoforms abolishes the binding between Tctp and Rheb, disrupting organ development. Depletion of 14-3-3s also reduces the level of phosphorylated S6 kinase, phosphorylated Thor/4E-BP and cyclin E (CycE). Growth defects from knockdown of 14-3-3 and Tctp are suppressed by CycE overexpression. This study suggests a novel mechanism of Tor regulation mediated by 14-3-3 interaction with Tctp and Rheb.
Highlights
14-3-3 family proteins regulate multiple signalling pathways
We have attempted to identify new genes interacting with translationally controlled tumour protein (Tctp) by searching for genetic modifiers of the reduced eye phenotype caused by Tctp RNA interference (RNAi) using Gal4/UAS system[36]
To further confirm the synergistic genetic interaction between Tctp and 14-3-3 genes, we tested whether Tctp RNAi eye phenotypes can be enhanced by 14-3-3 mutations, 14-3-3ej2B10 and 14-3-3z07103
Summary
14-3-3 family proteins regulate multiple signalling pathways. Understanding biological functions of 14-3-3 proteins has been limited by the functional redundancy of conserved isotypes. In Drosophila, Tctp is required for organ growth by promoting Rheb function for Tor signalling as a guanine nucleotide exchange factor[8]. Drosophila Tctp rescues embryonic lethality and cell proliferation defects in Arabidopsis Tctp (AtTctp) loss-of-function mutant Consistent with this interspecies complementation, Drosophila Rheb interacts with Tctp and with the plant AtTctp[13]. We provide evidence that 14-3-3 proteins are required for promoting the interaction between Tctp and Rheb Loss of both 14-3-3 isoforms critically impairs organ development, and such defects are strongly suppressed by CycE. Our data suggest that 14-3-3 proteins regulate the interaction between Tctp and Rheb for organ growth, providing novel insights into their functions in Tor signalling
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