Related Experiment Video

Updated: Mar 9, 2026

Evaluation of Substrate Ubiquitylation by E3 Ubiquitin-ligase in Mammalian Cell Lysates
09:47

Evaluation of Substrate Ubiquitylation by E3 Ubiquitin-ligase in Mammalian Cell Lysates

Published on: May 10, 2022

3.2K

The pseudophosphatase STYX targets the F-box of FBXW7 and inhibits SCFFBXW7 function

Veronika Reiterer1,2, Cristina Figueras-Puig2, Francois Le Guerroue3

  • 1Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.

The EMBO Journal
|December 24, 2016
PubMed

Insights

The pseudophosphatase STYX directly inhibits the tumor suppressor FBXW7 by blocking its SCF complex recruitment. This STYX-FBXW7 interaction impacts cancer patient prognosis and presents a potential drug target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • FBXW7 is a crucial tumor suppressor and the substrate-recruiting subunit of SCF ubiquitin ligase, vital for regulating cell proliferation and survival.
  • Loss of FBXW7 function leads to the stabilization of proteins promoting cell growth, contributing to various human malignancies.
  • Proteins directly regulating FBXW7 function remain largely uncharacterized, highlighting a gap in understanding its tumor-suppressive mechanisms.

Purpose of the Study:

  • To identify and characterize proteins that directly regulate the function of the F-box protein FBXW7.
  • To investigate the functional interaction between the pseudophosphatase STYX and FBXW7.
  • To explore the potential of the STYX-FBXW7 interaction as a therapeutic target in cancer.

Main Methods:

  • Proteomic analysis to map the interactome of STYX.
  • Biochemical assays to confirm the binding interaction between STYX and FBXW7.
  • Analysis of STYX and FBXW7 protein levels in breast cancer patient cohorts.

Main Results:

  • The STYX interactome includes several F-box proteins, notably FBXW7.
  • STYX binds to the F-box domain of FBXW7, inhibiting its incorporation into the SCF complex.
  • STYX acts as a direct inhibitor of FBXW7, leading to altered cellular levels of FBXW7 substrates.
  • STYX and FBXW7 levels are inversely correlated in breast cancer patients, correlating with disease prognosis.

Conclusions:

  • STYX directly inhibits FBXW7 by preventing its assembly into the SCF ubiquitin ligase complex.
  • The STYX-FBXW7 interaction modulates the stability of FBXW7 substrates, impacting cancer cell biology.
  • The inverse correlation between STYX and FBXW7 in breast cancer suggests their interaction influences disease progression.
  • Targeting the STYX-FBXW7 interaction offers a potential therapeutic strategy for cancers associated with FBXW7 dysfunction.
Keywords:
Cullin–RING ubiquitin ligaseF‐box proteinbreast cancermass spectrometrypseudophosphatase

More Related Videos

Assessing Cellular Target Engagement by SHP2 PTPN11 Phosphatase Inhibitors08:45

Assessing Cellular Target Engagement by SHP2 PTPN11 Phosphatase Inhibitors

Published on: July 17, 2020

6.7K
Evaluation of LC3-II Release via Extracellular Vesicles in Relation to the Accumulation of Intracellular LC3-positive Vesicles06:58

Evaluation of LC3-II Release via Extracellular Vesicles in Relation to the Accumulation of Intracellular LC3-positive Vesicles

Published on: October 18, 2024

1.3K

Related Concept Videos

The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
13.5K
Anaphase Promoting Complex00:50

Anaphase Promoting Complex

The stepwise destruction of specific proteins is necessary for the progression and completion of the cell cycle. Such proteins are ubiquitinated by ubiquitin ligases and then subsequently destroyed by the proteasome. The SCF (Skp1/Cullin/F-box) and the anaphase-promoting complex (APC) are two important ubiquitin ligases involved in cell cycle progression. While SCF is active throughout the cell cycle, APC gets activated during metaphase to anaphase transition. Cdc20 or Cdh1 binds to APC and...
3.5K
Actin Filament Depolymerization01:19

Actin Filament Depolymerization

Actin filaments (F-actin) are composed of actin subunits. The dissociation of actin monomers can occur from either end of F-actin. The rate of dissociation is faster from the minus-end or the pointed end, where the actin subunits exist with a bound ADP, together known as ADP-actin. The depolymerization of F-actin is aided by proteins, including the actin-depolymerizing factor (ADF) and cofilin family of proteins, gelsolin, and glia maturation factor (GMF).
In F-actin, the ADF/cofilin proteins...
4.1K
Mechanism of Filopodia Formation01:39

Mechanism of Filopodia Formation

Filopodia are thin, actin-rich cellular protrusions that play an important role in many fundamental cellular functions. They vary in their occurrence, length, and positioning in different cell types, suggesting their diverse roles.
Their main function is to guide migrating cells during normal tissue morphogenesis or cancer metastasis by recognizing and making initial contacts with the extracellular matrix. However, they can also act as stationary cell anchors or help to establish communication...
3.3K
Protein Complexes with Interchangeable Parts01:57

Protein Complexes with Interchangeable Parts

Groups of proteins may form a complex where each protein in this complex has a different role in the overall execution of the complex’s function. Often some of the proteins in the complex can be replaced by a closely related variant to give a complex that contains many of the same components yet is functionally distinct.
The SCF ubiquitin ligase is a protein complex of five individual proteins. This complex attaches ubiquitin to other target proteins to mark them for degradation. In order...
3.0K
Hedgehog Signaling Pathway02:33

Hedgehog Signaling Pathway

The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...
10.3K