Related Experiment Video

Updated: Oct 12, 2025

Characterization of Cell Membrane Extensions and Studying Their Roles in Cancer Cell Adhesion Dynamics
08:11

Characterization of Cell Membrane Extensions and Studying Their Roles in Cancer Cell Adhesion Dynamics

Published on: March 26, 2018

8.5K

MEKK5 Interacts with and Negatively Regulates the E3 Ubiquitin Ligase NEDD4 for Mediating Lung Cancer Cell Migration

Aiqin Sun1, Jun Zhu1, Song Xia1

  • 1School of Medicine, Jiangsu University, Zhenjiang 212013, China.

Life (Basel, Switzerland)
|November 27, 2021
PubMed

Insights

The kinase MEKK5 negatively regulates the E3 ubiquitin ligase NEDD4-mediated ubiquitination and lung cancer cell migration. This study clarifies MEKK5's inhibitory role in NEDD4 ubiquitination processes.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Biochemistry

Background:

  • The HECT E3 ubiquitin ligase NEDD4 and kinase MEKK5 are crucial for lung cancer cell migration.
  • Previous reports suggest MEKK5 may be ubiquitinated by NEDD4, but this interaction is uncharacterized.

Purpose of the Study:

  • To investigate the interaction between MEKK5 and NEDD4.
  • To determine if NEDD4 ubiquitinates MEKK5.
  • To elucidate the role of MEKK5 in NEDD4-mediated ubiquitination and lung cancer cell migration.

Main Methods:

  • Co-immunoprecipitation assays to confirm protein interaction.
  • GST-pulldown assays to identify interaction domains.
  • Ubiquitination assays to assess substrate and regulatory roles.
  • Cell migration assays to evaluate functional impact.

Main Results:

  • NEDD4 interacts with MEKK5 via its WW3 domain.
  • MEKK5 is not ubiquitinated by NEDD4; instead, it negatively regulates NEDD4-mediated ubiquitination.
  • Overexpression of MEKK5 significantly reduced NEDD4-promoted lung cancer cell migration.

Conclusions:

  • MEKK5 directly interacts with NEDD4.
  • MEKK5 acts as a negative regulator of NEDD4-mediated ubiquitination.
  • MEKK5 inhibits NEDD4-driven lung cancer cell migration, defining a novel inhibitory mechanism.
Keywords:
E3 ubiquitin ligaseMEKK5NEDD4cell migrationubiquitination

More Related Videos

The Soft Agar Colony Formation Assay08:01

The Soft Agar Colony Formation Assay

Published on: October 27, 2014

112.5K
An Immunofluorescent Method for Characterization of Barrett’s Esophagus Cells08:54

An Immunofluorescent Method for Characterization of Barrett’s Esophagus Cells

Published on: July 20, 2014

14.2K

Related Concept Videos

Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR...
2.3K
Cancer Cell Migration through Invadopodia01:35

Cancer Cell Migration through Invadopodia

Invadosome is a broad category of cell surface structures with proteolytic activity that  degrades the extracellular matrix (ECM). Invadosomes are present in normal cell types, including macrophages, endothelial cells, and neurons, as well as tumor cells. Although the macrophage podosomes and tumor cell invadopodia are classified as invadosomes, they have different structures, molecular pathways, and functions. Podosomes are short structures that last for a few minutes. However,...
2.5K
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...
7.0K
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.
36.5K
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.
2.3K
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...
4.7K