Related Experiment Video

Updated: May 25, 2026

Dissection of Drosophila Ovaries
04:55

Dissection of Drosophila Ovaries

Published on: October 19, 2006

Foxo3a transcription factor is a negative regulator of Skp2 and Skp2 SCF complex

J Wu1, S-W Lee, X Zhang

  • 1State Key Laboratory of Oncology in South China and Department of Experimental Research, Sun Yat-Sen University Cancer Center, Guangzhou, China.

Oncogene
|February 8, 2012
PubMed

Insights

Foxo3a suppresses cancer by inhibiting Skp2 SCF complex formation and activity. This transcription factor acts both by reducing Skp2 gene expression and by directly disrupting the Skp2 complex, repressing oncogenic activity.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cell Biology

Background:

  • Skp2 (S-phase kinase-associated protein-2) SCF complex is an E3 ligase crucial for cell cycle regulation and tumorigenesis.
  • Skp2 overexpression is common in human cancers, highlighting its oncogenic role.
  • Mechanisms regulating Skp2 SCF complex activity remain incompletely understood.

Purpose of the Study:

  • To identify novel regulators of the Skp2 SCF complex.
  • To elucidate the role of Foxo3a in regulating Skp2 SCF complex activity and function.
  • To investigate the tumor suppressive mechanisms of Foxo3a in relation to Skp2.

Main Methods:

  • Analysis of Skp2 gene expression regulation by Foxo3a.
  • Investigation of Foxo3a's direct interaction with Skp2.
  • Assessment of Skp2 SCF complex integrity and E3 ligase activity upon Foxo3a modulation.
  • Evaluation of p27 stability and oncogenic Skp2 activity in the presence of Foxo3a.

Main Results:

  • Foxo3a acts as a transcriptional repressor of Skp2 gene expression by binding to the Skp2 promoter.
  • Foxo3a directly interacts with Skp2, disrupting Skp2 SCF complex formation and inhibiting its E3 ligase activity.
  • Foxo3a promotes p27 stability and represses the oncogenic activity of Skp2.
  • Foxo3a demonstrates tumor suppressive functions through both transcription-dependent and independent mechanisms.

Conclusions:

  • Foxo3a is a novel negative regulator of the Skp2 SCF complex.
  • Foxo3a suppresses tumorigenesis via dual mechanisms: transcriptional repression of Skp2 and direct disruption of the Skp2 complex.
  • These findings establish a new role for Foxo3a in tumor suppression and provide insights into Skp2 SCF complex regulation.

More Related Videos

HOX Loci Focused CRISPR/sgRNA Library Screening Identifying Critical CTCF Boundaries10:10

HOX Loci Focused CRISPR/sgRNA Library Screening Identifying Critical CTCF Boundaries

Published on: March 31, 2019

Tropomodulin 3 Overexpression as a Marker for Platinum Resistance and Immune Infiltration in Ovarian Cancer09:40

Tropomodulin 3 Overexpression as a Marker for Platinum Resistance and Immune Infiltration in Ovarian Cancer

Published on: August 2, 2024

Related Concept Videos

Master Transcription Regulators02:23

Master Transcription Regulators

Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a  complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
Master Transcription Regulators02:23

Master Transcription Regulators

Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a  complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
Co-activators and Co-repressors02:04

Co-activators and Co-repressors

Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
Co-activators and Co-repressors02:04

Co-activators and Co-repressors

Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
Negative Regulator Molecules01:23

Negative Regulator Molecules

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.
Regulation of Expression at Multiple Steps01:23

Regulation of Expression at Multiple Steps

The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the addition of a...