Related Experiment Video
Updated: Aug 25, 2025
10:59
Label-Free Imaging of Lipid Storage Dynamics in Caenorhabditis elegans using Stimulated Raman Scattering Microscopy
Published on: May 28, 2021
4.3K
DCAF7 regulates cell proliferation through IRS1-FOXO1 signaling
Scott Frendo-Cumbo1,2, Taoyingnan Li1,3, Dustin A Ammendolia1,3
1Cell Biology Program, Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.
Iscience
|October 17, 2022
Summary
Researchers identified DCAF7 as a key regulator of cell proliferation. DCAF7 influences cell cycle progression by interacting with IRS1 and affecting FOXO1 activity, impacting organism growth.
Area of Science:
- Cell Biology
- Molecular Biology
- Genetics
Background:
- Cell proliferation is crucial for growth and is regulated by growth factors like insulin and IGF1.
- IRS1 is the primary mediator of insulin/IGF1 signaling pathways.
- Identifying IRS1 interactors is key to understanding cell proliferation control.
Purpose of the Study:
- To identify novel interactors of IRS1 that regulate cell proliferation.
- To elucidate the role of DCAF7 in insulin/IGF1 signaling and cell cycle control.
- To investigate the conserved function of DCAF7 in organismal growth.
Main Methods:
- Proximity-dependent biotin identification (BioID) was used to identify IRS1-interacting proteins.
- DCAF7 knockdown experiments were performed in HepG2 cells and *Drosophila melanogaster*.
- Analysis included cell proliferation assays, cell cycle analysis, Western blotting for AKT phosphorylation, and transcription factor localization studies.
Main Results:
- BioID identified 40 proximal interactors of IRS1, including DCAF7.
- DCAF7 knockdown in HepG2 cells inhibited cell proliferation by causing G2 cell cycle arrest.
- DCAF7 is necessary for insulin-stimulated AKT phosphorylation and its absence leads to FOXO1 nuclear localization and G2 cell cycle inhibition.
- Knockdown of DCAF7 homolog (wap) in *Drosophila* resulted in reduced wing size and cell number, which was rescued by concurrent knockdown of *dfoxo*.
Conclusions:
- DCAF7 acts as a critical regulator of cell proliferation and cell cycle progression.
- DCAF7 mediates its effects through the IRS1-FOXO1 signaling axis.
- The identified signaling pathway is conserved and relevant to whole organism growth.
Related Concept Videos
01:22PI3K/mTOR/AKT Signaling Pathway
3.8K
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...
3.8K
02:34Inhibition of Cdk Activity
4.9K
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...
4.9K
03:03mTOR Signaling and Cancer Progression
3.9K
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...
The mTOR pathway or the...
3.9K
01:27Molecular Factors Affecting Cell Division
3.2K
Several external and internal factors influence the initiation and inhibition of cell division. For instance, the death of nearby cells or the release of human growth hormone (hGH) promotes cell division. In contrast, lack of hGH or crowding of cells can inhibit cell division.
Several proteins function as internal regulators to ensure each cell cycle stage is completed faithfully before proceeding to the next. Regulator molecules may act directly or influence the activity or production of other...
Several proteins function as internal regulators to ensure each cell cycle stage is completed faithfully before proceeding to the next. Regulator molecules may act directly or influence the activity or production of other...
3.2K
02:23Abnormal Proliferation
4.6K
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.6K
01:23Negative Regulator Molecules
35.6K
Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
35.6K