Related Experiment Video

Updated: Dec 31, 2025

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
06:54

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells

Published on: October 27, 2020

14.1K

Structure and regulation of human epithelial cell transforming 2 protein

Mengran Chen1,2,3, Han Pan1,2, Lingfei Sun2

  • 1Ministry of Education Key Laboratory of Protein Science, Tsinghua University, Beijing 100084, China.

Proceedings of the National Academy of Sciences of the United States of America
|January 1, 2020
PubMed

Insights

Epithelial cell transforming 2 (Ect2) protein regulates cell division and is implicated in cancer. We discovered Ect2

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • Epithelial cell transforming 2 (Ect2) protein is a key regulator of Rho GTPases, essential for cytokinesis and other cellular functions.
  • Dysregulation of Ect2 is frequently observed in various types of cancer, highlighting its role in tumorigenesis.

Purpose of the Study:

  • To elucidate the structural and mechanistic basis of Ect2 regulation.
  • To investigate how cancer-associated mutations affect Ect2 function and regulation.

Main Methods:

  • X-ray crystallography to determine the structure of human Ect2.
  • Biochemical assays, including Förster resonance energy transfer (FRET) and hydrogen-deuterium exchange mass spectrometry (HDX-MS), to analyze Ect2-RhoA interactions.
  • In vitro and in vivo studies to assess the impact of cancer mutations on Ect2 activity.

Main Results:

  • The crystal structure reveals that the C-terminal PH domain of Ect2 autoinhibits the enzyme by blocking the RhoA-binding site.
  • Ect2 activation occurs through an allosteric mechanism involving GTP-bound RhoA binding to the PH domain, creating a positive-feedback loop for RhoA signaling.
  • Recurrent cancer mutations identified at regulatory and catalytic interfaces were shown to dysregulate Ect2 activity.

Conclusions:

  • Ect2 autoinhibition by its PH domain provides a novel regulatory mechanism.
  • The allosteric activation by RhoA suggests a sophisticated feedback loop in RhoA signaling.
  • Understanding Ect2 regulation and the impact of cancer mutations offers insights into therapeutic strategies for Ect2-driven cancers.
Keywords:
Ect2RhoAbiophysicscancercytokinesis

More Related Videos

Induction and Analysis of Epithelial to Mesenchymal Transition10:37

Induction and Analysis of Epithelial to Mesenchymal Transition

Published on: August 27, 2013

36.4K
Phospholipid Mediator Induced Transformation in Three-Dimensional Cultures08:02

Phospholipid Mediator Induced Transformation in Three-Dimensional Cultures

Published on: July 27, 2022

2.9K

Related Concept Videos

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...
10.3K
Cadherins in Tissue Organization01:19

Cadherins in Tissue Organization

The cadherins are a superfamily of cell adhesion molecules comprising over 180 variants, with specific tissues expressing a particular combination of cadherin types. Cadherins generally exhibit homophilic binding; i.e., cadherins on one cell bind to cadherins of the same or closely related type on another cell. Thus, cells of the same type have a specific affinity to bind to each other and sort themselves into clusters to form tissues.
Cell Sorting During Development
Cell sorting plays an...
3.8K
Abnormal Proliferation02:23

Abnormal Proliferation

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...
5.0K
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.
38.1K
Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
7.6K
Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal01:22

Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal

Erythropoietin-producing hepatocellular carcinoma receptor (Eph) and its ligand, Eph receptor-interacting protein (Ephrin) were first discovered in the human carcinoma cell line, hence the name. Ephrin-Eph interaction guides cells to reach their appropriate location in adult tissues. They also play an essential role in the immune system by helping in immune cell migration, adhesion, and activation. Based on their structure and function, Eph is divided into two classes — EphA and EphB.
2.6K