Related Experiment Video

Updated: Sep 28, 2025

Dissection of Drosophila Ovaries
04:55

Dissection of Drosophila Ovaries

Published on: October 19, 2006

49.8K

Tctp regulates the level and localization of Foxo for cell growth in Drosophila

Sujin Nam1, Thao Phuong Le1,2, SeYeon Chung3

  • 1Department of Biological Sciences, Korea Advanced Institute of Science & Technology, 291 Daehak-ro, Yuseong-gu, Daejeon, 34141, Korea.

Cell Death Discovery
|April 1, 2022
PubMed

Insights

Drosophila Translationally controlled tumor protein (Tctp) and 14-3-3ε regulate organ size by controlling Foxo protein levels and localization, impacting cell growth. This suggests a conserved role for TCTP in human cells.

Area of Science:

  • Cell biology
  • Developmental biology
  • Molecular genetics

Background:

  • Cell size regulation is vital for proper organ development.
  • Insulin signaling influences organ size by modulating Foxo transcription factors via 14-3-3 proteins in Drosophila.
  • The precise mechanisms governing Foxo levels and nuclear localization in developing organs remain unclear.

Purpose of the Study:

  • To investigate the roles of Drosophila Translationally controlled tumor protein (Tctp) and its partner 14-3-3 in regulating Foxo during organ development.
  • To elucidate how Tctp influences Foxo levels and localization, and its impact on cell growth and organ size.
  • To explore the conserved function of TCTP in regulating FOXO in human cells.

Main Methods:

  • Overexpression and knockdown of Tctp and Foxo in Drosophila eye discs and salivary glands.
  • Analysis of Foxo protein levels and subcellular localization using genetic manipulation.
  • Assessment of organ size and cell size, including defects in endoreplication.
  • Investigating TCTP's role in human HeLa cells by knocking down human TCTP and observing FOXO1 levels.

Main Results:

  • Tctp overexpression antagonizes Foxo's growth-inhibitory effects by reducing Foxo levels in the eye disc.
  • Foxo overexpression or Tctp knockdown in salivary glands reduces gland size due to smaller cell size and impaired endoreplication.
  • 14-3-3ε knockdown mimics Foxo overexpression effects, indicating an isoform-specific role for 14-3-3.
  • Tctp overexpression restores cytoplasmic mislocalization of overexpressed Foxo, while Tctp knockdown increases cytoplasmic Foxo and decreases nuclear Foxo.
  • Knockdown of human TCTP increases cytoplasmic FOXO1 levels in HeLa cells, suggesting conserved regulation.

Conclusions:

  • Tctp and 14-3-3ε are critical for cell growth, acting by reducing cytoplasmic Foxo levels.
  • Tctp plays a significant role in controlling Foxo protein levels and localization, thereby influencing organ development.
  • The findings suggest a conserved mechanism for TCTP in regulating FOXO proteins across species, with implications for human cell biology.

More Related Videos

A Cell-based Assay to Investigate Non-muscle Myosin II Contractility via the Folded-gastrulation Signaling Pathway in Drosophila S2R+ Cells07:15

A Cell-based Assay to Investigate Non-muscle Myosin II Contractility via the Folded-gastrulation Signaling Pathway in Drosophila S2R+ Cells

Published on: August 19, 2018

7.6K
Induction and Diagnosis of Tumors in Drosophila Imaginal Disc Epithelia08:14

Induction and Diagnosis of Tumors in Drosophila Imaginal Disc Epithelia

Published on: July 25, 2017

15.3K

Related Concept Videos

Canonical Wnt Signaling Pathway02:54

Canonical Wnt Signaling Pathway

The gene encoding the main signaling molecules of the Wnt signaling pathways (the Wnt proteins) was discovered almost four decades ago by Nüsslein-Volhard and Wieschaus. They identified and originally named the gene "wingless" (wg) after a phenotype discovered during their landmark genetic screen in Drosophila for body pattern defects. At around the same time, another researcher named Harold Varmus found that a murine tumor virus activates the mammalian wg homolog, Int-1, which...
9.1K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
3.9K
TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
7.8K
Role Of Notch Signalling In Intestinal Stem Cell Renewal01:12

Role Of Notch Signalling In Intestinal Stem Cell Renewal

Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
2.2K
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
5.0K
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
4.1K