Related Experiment Video

Updated: Jul 14, 2026

Immunofluorescence Analysis of Endogenous and Exogenous Centromere-kinetochore Proteins
05:35

Immunofluorescence Analysis of Endogenous and Exogenous Centromere-kinetochore Proteins

Published on: March 3, 2016

DCAFs, the missing link of the CUL4-DDB1 ubiquitin ligase

Jennifer Lee1, Pengbo Zhou

  • 1Department of Pathology and Laboratory Medicine, Weill Medical College of Cornell University, New York, NY 10021, USA.

Molecular Cell
|June 26, 2007
PubMed

Insights

The CUL4-DDB1 ubiquitin ligase controls crucial cell functions. New research identifies DDB1 and CUL4-associated factors (DCAFs) as key receptors, revealing how this system targets specific proteins.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • The CUL4-DDB1 complex is a ubiquitin ligase vital for regulating cell proliferation, survival, DNA repair, and genomic integrity.
  • The specific substrate receptors that confer substrate specificity to the CUL4-DDB1 ligase have remained largely unidentified.
  • Understanding these receptors is crucial for deciphering the complex regulatory roles of CUL4-DDB1.

Purpose of the Study:

  • To identify the substrate receptors of the CUL4-DDB1 ubiquitin ligase complex.
  • To elucidate the mechanisms by which CUL4-DDB1 achieves substrate specificity.
  • To expand the understanding of cellular processes regulated by CUL4-DDB1.

Main Methods:

  • Utilized biochemical assays to investigate protein-protein interactions.
  • Employed genetic approaches to identify functional components of the CUL4-DDB1 complex.
  • Characterized the role of newly identified factors in CUL4-DDB1-mediated ubiquitination.

Main Results:

  • Identified a family of DDB1 and CUL4-associated factors (DCAFs) as the substrate receptors for CUL4-DDB1.
  • Demonstrated that DCAFs dictate the substrate specificity of the CUL4-DDB1 ubiquitin ligase.
  • Showcased the involvement of DCAFs in a wide array of cellular processes.

Conclusions:

  • DCAFs are essential components that confer substrate specificity to the CUL4-DDB1 ubiquitin ligase.
  • The identification of DCAFs significantly advances our understanding of CUL4-DDB1 regulation.
  • This discovery implicates CUL4-DDB1-DCAF complexes in diverse cellular functions, opening new avenues for research.

More Related Videos

Using In Vitro Fluorescence Resonance Energy Transfer to Study the Dynamics Of Protein Complexes at a Millisecond Time Scale10:50

Using In Vitro Fluorescence Resonance Energy Transfer to Study the Dynamics Of Protein Complexes at a Millisecond Time Scale

Published on: March 14, 2019

In Vitro Analysis of E3 Ubiquitin Ligase Function06:06

In Vitro Analysis of E3 Ubiquitin Ligase Function

Published on: May 14, 2021

Related Concept Videos

Anaphase Promoting Complex00:50

Anaphase Promoting Complex

The stepwise destruction of specific proteins is necessary for the progression and completion of the cell cycle. Such proteins are ubiquitinated by ubiquitin ligases and then subsequently destroyed by the proteasome. The SCF (Skp1/Cullin/F-box) and the anaphase-promoting complex (APC) are two important ubiquitin ligases involved in cell cycle progression. While SCF is active throughout the cell cycle, APC gets activated during metaphase to anaphase transition. Cdc20 or Cdh1 binds to APC and...
Anaphase Promoting Complex00:50

Anaphase Promoting Complex

The stepwise destruction of specific proteins is necessary for the progression and completion of the cell cycle. Such proteins are ubiquitinated by ubiquitin ligases and then subsequently destroyed by the proteasome. The SCF (Skp1/Cullin/F-box) and the anaphase-promoting complex (APC) are two important ubiquitin ligases involved in cell cycle progression. While SCF is active throughout the cell cycle, APC gets activated during metaphase to anaphase transition. Cdc20 or Cdh1 binds to APC and...
Protein Complexes with Interchangeable Parts01:57

Protein Complexes with Interchangeable Parts

Groups of proteins may form a complex where each protein in this complex has a different role in the overall execution of the complex’s function. Often some of the proteins in the complex can be replaced by a closely related variant to give a complex that contains many of the same components yet is functionally distinct.
The SCF ubiquitin ligase is a protein complex of five individual proteins. This complex attaches ubiquitin to other target proteins to mark them for degradation. In order to...
Covalently Linked Protein Regulators02:04

Covalently Linked Protein Regulators

Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein.
Covalently Linked Protein Regulators02:04

Covalently Linked Protein Regulators

Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein.
Export of Misfolded Proteins out of the ER01:32

Export of Misfolded Proteins out of the ER

After folding, the ER assesses the quality of secretory and membrane proteins. The correctly folded proteins are cleared by the calnexin cycle for transport to their final destination, while misfolded proteins are held back in the ER lumen. The ER chaperones attempt to unfold and refold the misfolded proteins but sometimes fail to achieve the correct native conformation. Such terminally misfolded proteins are then exported to the cytosol by ER-associated degradation or ERAD pathway for...