Related Experiment Video

Updated: Sep 8, 2025

Examining the Dynamics of Cellular Adhesion and Spreading of Epithelial Cells on Fibronectin During Oxidative Stress
10:57

Examining the Dynamics of Cellular Adhesion and Spreading of Epithelial Cells on Fibronectin During Oxidative Stress

Published on: October 13, 2019

7.6K

The complex of Fas-associated factor 1 with Hsp70 stabilizes the adherens junction integrity by suppressing RhoA

Soonhwa Song1, Joon Kyu Park2, Sang Chul Shin2

  • 1Graduate School of Pharmaceutical Sciences, College of Pharmacy, Ewha Womans University, Seoul 03760, Republic of Korea.

Journal of Molecular Cell Biology
|June 15, 2022
PubMed

Insights

Fas-associated factor 1 (FAF1) regulates cell junctions by forming a complex with Hsp70, preventing RhoA activation and maintaining tissue stability. This discovery offers a potential therapeutic target for inhibiting cancer metastasis.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • Fas-associated factor 1 (FAF1) is a scaffolding protein implicated in various diseases, including cancers.
  • FAF1 possesses multiple ubiquitin-related domains that mediate interactions with specific partners.
  • The interaction between FAF1's UBL1 domain and heat shock protein 70 (Hsp70) is linked to tumor formation, but its mechanism is unclear.

Purpose of the Study:

  • To elucidate the molecular mechanism underlying the interaction between FAF1 and Hsp70.
  • To investigate the role of the FAF1-Hsp70 complex in regulating cell-cell junctions and RhoA activation.
  • To determine the implications of FAF1 function in cancer progression and metastasis.

Main Methods:

  • Structural analysis to identify key residues involved in FAF1-Hsp70 interaction.
  • Biochemical assays to assess the formation and function of the FAF1-Hsp70-IQGAP1 complex.
  • 3D spheroid cell culture models to evaluate the impact of FAF1 depletion on cell invasion.

Main Results:

  • Structural analysis identified Histidine 160 (His160) of FAF1 as crucial for Hsp70 binding.
  • The FAF1-Hsp70 complex formation is essential for subsequent interaction with IQGAP1.
  • FAF1, through the FAF1-Hsp70-IQGAP1 complex, negatively regulates RhoA activation, thereby stabilizing cell-to-cell junctions.
  • FAF1 depletion enhanced collective invasion in 3D spheroid models, indicating a role in suppressing metastasis.

Conclusions:

  • FAF1 is a critical regulator of adherens junction integrity during tissue homeostasis and morphogenesis.
  • The FAF1-Hsp70 complex acts as a novel suppressor of RhoA activation, preventing downstream signaling that disrupts cell junctions.
  • The FAF1-Hsp70 complex presents a potential therapeutic target for inhibiting tumorigenesis and metastasis.
Keywords:
FAF1–Hsp70 complexIQGAP1RhoA activationX-ray crystallographyadherens junctionheat shock protein 70 (Hsp70)human Fas-associated factor 1 (FAF1)

More Related Videos

Aip1p Dynamics Are Altered by the R256H Mutation in Actin08:57

Aip1p Dynamics Are Altered by the R256H Mutation in Actin

Published on: July 30, 2014

8.1K
Affinity Precipitation of Active Rho-GEFs Using a GST-tagged Mutant Rho Protein GST-RhoAG17A from Epithelial Cell Lysates11:28

Affinity Precipitation of Active Rho-GEFs Using a GST-tagged Mutant Rho Protein GST-RhoAG17A from Epithelial Cell Lysates

Published on: March 31, 2012

16.7K

Related Concept Videos

Intracellular Signaling Affects Focal Adhesions01:17

Intracellular Signaling Affects Focal Adhesions

Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
2.8K
Adherens Junctions01:24

Adherens Junctions

Strong contact points between adjacent cells anchor them to each other, forming tissues. Such anchoring junctions are of two types –  adherens junctions and desmosomes. Adherens junctions are abundant in tissues such as  epithelium and endothelium, forming a continuous zone of adhesion called the adhesion belt. In other tissues, such as  heart muscle, they appear as clusters, linking the cells to produce coordinated heart muscle contraction.
Adherens Junctions are Dynamic
5.0K
Tension Response at Adherens Junctions01:26

Tension Response at Adherens Junctions

The adherens junctions that anchor cells together are multi-protein complexes that dynamically adapt to mechanical stimuli such as tensile forces and shear stress. Mechanosensory proteins in these junctions can sense such mechanical stimuli and undergo a shift in their conformation, resulting in an altered function — a process called mechanotransduction.
α-Catenin as a Mechanosensory Protein
The α-catenin of adherens junctions is an allosteric protein with three VH (vinculin...
2.8K
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...
2.5K
Small GTPases - Ras and Rho01:24

Small GTPases - Ras and Rho

Ras and Rho are small monomeric GTPases that act downstream of receptor tyrosine kinase (RTK) and regulate various cellular processes. These GTPases switch between active and inactive states by binding to guanine nucleotides.
Three regulatory proteins control their activity:
4.2K
Anchoring Junctions01:03

Anchoring Junctions

Anchoring junctions are multiprotein complexes that help cells connect to other cells and the extracellular matrix. Anchoring junctions are present on the lateral and basal surfaces of cells, providing strong and flexible connections. Focal adhesions are often formed due to cell interactions with the ECM substrata, which initiate signal transduction via kinase cascades and other mechanisms. Together, they provide stability and tissue integrity. There are three types of anchoring junctions:...
3.9K