Related Experiment Video

Updated: Aug 9, 2025

Reconstitution Of β-catenin Degradation In Xenopus Egg Extract
09:41

Reconstitution Of β-catenin Degradation In Xenopus Egg Extract

Published on: June 17, 2014

12.2K

Phosphomevalonate Kinase Controls β-Catenin Signaling via the Metabolite 5-Diphosphomevalonate

Zhiqiang Chen1,2, Xinyi Zhou1,2, Xiaojun Zhou1,2

  • 1Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Frontier Science Center for Immunology and Metabolism, TaiKang Center for Life and Medical Sciences, Wuhan University, Wuhan, 430072, P. R. China.

Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|February 22, 2023
PubMed

Insights

The mevalonate pathway enzyme PMVK stabilizes beta-catenin signaling, promoting cancer. Inhibiting PMVK with PMVKi5 shows promise for treating liver and colorectal cancers.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Oncology

Background:

  • Beta-catenin signaling is frequently dysregulated in various cancers.
  • The mevalonate pathway is crucial for cellular processes, but its role in beta-catenin regulation is not fully understood.

Purpose of the Study:

  • To investigate the role of the mevalonate pathway enzyme PMVK in regulating beta-catenin signaling.
  • To explore PMVK as a potential therapeutic target for cancer treatment.

Main Methods:

  • Genome-wide screening of the mevalonate pathway enzymes.
  • Biochemical assays to determine PMVK's mechanism of action on beta-catenin.
  • In vivo studies using mouse models for embryonic development and chemically induced carcinogenesis.
  • Development and testing of a small molecule inhibitor of PMVK (PMVKi5).

Main Results:

  • PMVK stabilizes beta-catenin through two mechanisms: MVA-5PP inhibiting CKIα and PMVK directly phosphorylating beta-catenin.
  • PMVK is essential for embryonic development, with PMVK deletion causing embryonic lethality.
  • PMVK deficiency in liver tissue reduces hepatocarcinogenesis.
  • PMVKi5 effectively inhibits liver and colorectal cancer progression in mouse models.

Conclusions:

  • PMVK plays a non-canonical role in stabilizing beta-catenin signaling, linking the mevalonate pathway to cancer.
  • PMVK is a critical regulator of embryonic development and hepatocarcinogenesis.
  • PMVK inhibition represents a novel therapeutic strategy for liver and colorectal cancers.
Keywords:
casein kinase Iαhepatocellular carcinomamevalonate 5-diphosphatephosphomevalonate kinaseβ-catenin

More Related Videos

A Mass Spectrometry-Based Approach to Identify Phosphoprotein Phosphatases and their Interactors10:17

A Mass Spectrometry-Based Approach to Identify Phosphoprotein Phosphatases and their Interactors

Published on: April 29, 2022

2.5K
Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay12:26

Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay

Published on: May 3, 2018

18.7K

Related Concept Videos

Catenins01:23

Catenins

Catenins are characterized by multiple binding domains and dynamic structures that allow them to function as linker proteins in cell junction complexes. All catenins, except α-catenin, contain a characteristic protein sequence called the armadillo repeat and are therefore also called armadillo proteins.
Catenins in Cell Junctions
Catenins bind to cell adhesion molecules such as cadherins and link them to different cytoskeletal proteins depending on the type of cell junction. At the...
2.4K
Protein Kinases and Phosphatases02:54

Protein Kinases and Phosphatases

Proteins undergo chemical modifications that trigger changes in the charge, structure, and conformation of the proteins. Phosphorylation, acetylation, glycosylation, nitrosylation, ubiquitination, lipidation, methylation, and proteolysis are various protein modifications that regulate protein activity. Such modifications are usually enzyme-driven.
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
13.3K
Calmodulin-dependent Signaling01:16

Calmodulin-dependent Signaling

Calmodulin (CaM) is a calcium-binding protein in eukaryotes that controls various calcium-regulated cellular processes. It has four calcium-binding sites that bind calcium to form the calcium-calmodulin ( Ca2+-CaM) complex. GPCR stimulation increases the calcium levels in the cells that bind to CaM and induces a conformational change.
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
5.2K
Amplifying Signals via Enzymatic Cascade01:22

Amplifying Signals via Enzymatic Cascade

When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze...
8.6K
Phosphorylation01:02

Phosphorylation

The addition or removal of phosphate groups from proteins is the most common chemical modification that regulates cellular processes. These modifications can affect the structure, activity, stability, and localization of proteins within cells as well as their interactions with other proteins.
During phosphorylation, protein kinases transfer the terminal phosphate group of ATP to specific amino acid side chains of substrate proteins. Serine, threonine, and tyrosine are the most commonly...
50.7K
Canonical Wnt Signaling Pathway02:54

Canonical Wnt Signaling Pathway

The gene encoding the main signaling molecules of the Wnt signaling pathways (the Wnt proteins) was discovered almost four decades ago by Nüsslein-Volhard and Wieschaus. They identified and originally named the gene "wingless" (wg) after a phenotype discovered during their landmark genetic screen in Drosophila for body pattern defects. At around the same time, another researcher named Harold Varmus found that a murine tumor virus activates the mammalian wg homolog, Int-1, which...
8.8K