Related Experiment Video

Updated: Nov 9, 2025

Characterization of G Protein-coupled Receptors by a Fluorescence-based Calcium Mobilization Assay
11:49

Characterization of G Protein-coupled Receptors by a Fluorescence-based Calcium Mobilization Assay

Published on: July 28, 2014

41.1K

Switching DCAFs: Beyond substrate receptors

Sang-Min Jang1,2, Christophe E Redon1, Mirit I Aladjem1

  • 1Developmental Therapeutics Branch, Center for Cancer Research, NCI, NIH, Bethesda, Maryland, USA.

Bioessays : News and Reviews in Molecular, Cellular and Developmental Biology
|April 15, 2021
PubMed

Insights

DDB1-CUL4 Associated Factors (DCAFs) control cell processes by targeting proteins for degradation. Some DCAFs act as "structural" to localize complexes, enabling "catalytic" DCAFs to target specific proteins, regulating cell growth.

Area of Science:

  • Cellular Biology
  • Molecular Biology
  • Genetics

Background:

  • DDB1-CUL4 Associated Factors (DCAFs) are crucial for cellular homeostasis and disease.
  • Over 100 DCAFs associate with the Cullin-Ring Ubiquitin Ligase 4 (CRL4) complex, mediating substrate protein degradation.
  • DCAFs are traditionally viewed as substrate receptors dictating CRL4 specificity.

Purpose of the Study:

  • To investigate the dual role of DCAFs in CRL4 complex regulation.
  • To explore the proposed "DCAF switch" mechanism in controlling protein degradation.
  • To understand how DCAFs modulate cell cycle progression and genomic integrity.

Main Methods:

  • Bio-chemical assays to study DCAF-CRL4 interactions.
  • Cellular localization studies using microscopy.
  • Ubiquitination assays to assess substrate degradation.

Main Results:

  • Evidence suggests some DCAFs function structurally, localizing CRL4 complexes to specific cellular compartments.
  • CRL4 complexes dissociate from structural DCAFs before engaging with catalytic DCAFs.
  • This "DCAF switch" mechanism allows for precise spatial and temporal control of protein degradation.

Conclusions:

  • DCAF switches provide a novel mechanism for regulating protein degradation.
  • This mechanism is critical for controlling proteins involved in cell growth and proliferation.
  • Understanding DCAF function is key to deciphering cellular homeostasis and disease pathogenesis.
Keywords:
Cullin-Ring Ubiquitin Ligase 4 complexDCAF switchDDB1-CUL4 Associated Factorscatalytic DCAFsstructural DCAFs

More Related Videos

A Kinetic Fluorescence-based Ca2+ Mobilization Assay to Identify G Protein-coupled Receptor Agonists, Antagonists, and Allosteric Modulators07:41

A Kinetic Fluorescence-based Ca2+ Mobilization Assay to Identify G Protein-coupled Receptor Agonists, Antagonists, and Allosteric Modulators

Published on: February 20, 2018

9.1K
Visualizing the Conformational Dynamics of Membrane Receptors Using Single-Molecule FRET10:59

Visualizing the Conformational Dynamics of Membrane Receptors Using Single-Molecule FRET

Published on: August 17, 2022

3.5K

Related Concept Videos

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...
14.9K
Transducer Mechanism: G Protein–Coupled Receptors01:30

Transducer Mechanism: G Protein–Coupled Receptors

G Protein–Coupled Receptors (GPCRs) are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to various stimuli. GPCRs regulate critical physiological pathways and are excellent drug targets for treating diseases such as diabetes, cancer, obesity, depression, or Alzheimer's. Nearly 35% of approved drugs implement their therapeutic effects by selectively interacting with specific GPCRs.
GPCRs are also called heptahelical,...
3.1K
GPCR Desensitization01:12

GPCR Desensitization

G protein-coupled receptor (GPCR) signaling plays a crucial role in cell functioning. GPCR desensitization is an equally essential process. It allows cells to respond to changing environments and regain sensitivity to new stimuli while preventing unnecessary stimulation when no longer needed. Prolonged exposure to stimuli leads to GPCR desensitization. It involves blocking the receptors from binding and activating additional G proteins. This inhibits activation of downstream effectors, thereby...
7.1K
GPCRs Regulate Adenylyl Cylase Activity01:09

GPCRs Regulate Adenylyl Cylase Activity

Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of...
6.3K
Assembly of Signaling Complexes01:30

Assembly of Signaling Complexes

Multiprotein signaling complexes are formed in a dynamic process involving protein-protein interactions at the cytoplasmic domain of transmembrane receptors or enzymatic and non-enzymatic proteins associated with the receptor. These complexes ensure the activation and propagation of intracellular signals that regulate cell functions.
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
6.1K
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...
6.1K