Related Experiment Video

Updated: Aug 11, 2026

Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries
08:49

Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries

Published on: January 22, 2019

Beryllium toxicity. The selective inhibition of casein kinase 1

B Cummings, M R Kaser, G Wiggins

    The Biochemical Journal
    |October 15, 1982
    PubMed

    Insights

    Beryllium (Be2+) inhibits casein kinase 1 in liver cytoplasm and nuclei. This enzyme inhibition was observed in vitro and in vivo following Be2+ administration in rats, impacting liver regeneration.

    Area of Science:

    • Biochemistry
    • Molecular Biology
    • Toxicology

    Background:

    • Casein kinase 1 (CK1) is a crucial enzyme involved in various cellular processes.
    • Beryllium (Be2+) is a toxic metal with known health effects.
    • Understanding the molecular targets of beryllium toxicity is essential for assessing its health risks.

    Purpose of the Study:

    • To investigate the in vitro and in vivo effects of beryllium (Be2+) on casein kinase 1 (CK1) activity.
    • To determine the kinetic mechanism of CK1 inhibition by Be2+.
    • To assess the impact of Be2+ on CK1 activity in the context of liver regeneration.

    Main Methods:

    • In vitro enzyme assays using purified casein kinase 1 (CK1) and casein as a substrate.
    • Kinetic analysis to determine inhibition constants (Ki) and mechanism.
    • Administration of lethal doses (LD50) of Be2+ to rats and subsequent analysis of liver enzyme activity.

    Main Results:

    • Beryllium (Be2+) significantly inhibited both cytoplasmic and nuclear casein kinase 1 (CK1) in vitro.
    • CK1 inhibition by Be2+ was competitive with respect to the protein substrate and non-competitive with respect to ATP.
    • In vivo, Be2+ administration reduced CK1 activity in the livers of rats, particularly in partially hepatectomized animals.

    Conclusions:

    • Casein kinase 1 (CK1) is a direct molecular target of beryllium (Be2+) toxicity.
    • Be2+-induced inhibition of CK1 may contribute to the observed toxic effects of beryllium, potentially impacting cellular processes like liver regeneration.

    More Related Videos

    Identification of Novel CK2 Kinase Substrates Using a Versatile Biochemical Approach11:11

    Identification of Novel CK2 Kinase Substrates Using a Versatile Biochemical Approach

    Published on: February 21, 2019

    Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs10:44

    Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs

    Published on: May 15, 2019

    Related Concept Videos

    Inhibition of Cdk Activity02:34

    Inhibition of Cdk Activity

    The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
    Targeted Cancer Therapies02:57

    Targeted Cancer Therapies

    The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
    There are several types of targeted therapies against specific...
    Allosteric Proteins-ATCase01:19

    Allosteric Proteins-ATCase

    Binding sites linkages can regulate a protein's function.  For example, enzyme activity is often regulated through a feedback mechanism where the end product of the biochemical process serves as an inhibitor.
    Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to  N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis pathway,...
    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,...