14-3-3 proteins regulate Tctp-Rheb interaction for organ growth in Drosophila
Thao Phuong Le1, Linh Thuong Vuong1, Ah-Ram Kim1
1Department of Biological Sciences, Korea Advanced Institute of Science and Technology, 291 Daehak-ro, Yuseong-gu, Daejeon 305-701, Korea.
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.
Insights
14-3-3 proteins regulate Tor signaling by interacting with Tctp and Rheb in Drosophila. This interaction is crucial for tissue growth and organ development, revealing a new regulatory mechanism.
Area of Science:
- Cellular signaling pathways
- Molecular biology
- Developmental biology
Background:
- 14-3-3 proteins are crucial regulators of diverse signaling pathways.
- Functional redundancy among 14-3-3 protein isotypes has limited understanding of their specific roles.
- Tor signaling is a key pathway controlling cell growth and proliferation.
Purpose of the Study:
- To investigate the role of 14-3-3 proteins in Tor signaling.
- To elucidate the interaction between 14-3-3 proteins, Tctp, and Rheb.
- To understand the impact of this interaction on Drosophila organ development and tissue growth.
Main Methods:
- Genetic interaction studies in Drosophila.
- Protein-protein interaction assays.
- Analysis of signaling pathway components (e.g., phosphorylated S6 kinase, Thor/4E-BP, cyclin E).
- Gene knockdown and overexpression experiments.
Main Results:
- 14-3-3 proteins physically interact with Tctp and Rheb.
- Knockdown of 14-3-3 isoforms disrupts Tctp-Rheb binding and impairs organ development.
- Depletion of 14-3-3 proteins reduces key Tor pathway components and cyclin E levels.
- Overexpression of cyclin E rescues growth defects caused by 14-3-3 and Tctp knockdown.
Conclusions:
- 14-3-3 proteins mediate Tor signaling through interaction with Tctp and Rheb.
- This interaction is essential for Drosophila tissue growth and organ development.
- A novel mechanism for Tor pathway regulation involving 14-3-3 proteins is proposed.
Related Concept Videos
PI3K/mTOR/AKT Signaling Pathway
Negative Regulator Molecules
mTOR Signaling and Cancer Progression
The mTOR pathway or the...
TGF - β Signaling Pathway
Canonical Wnt Signaling Pathway
Small GTPases - Ras and Rho
Three regulatory proteins control their activity:


