Related Experiment Video

Updated: Oct 13, 2026

In Vitro Analysis of E3 Ubiquitin Ligase Function
06:06

In Vitro Analysis of E3 Ubiquitin Ligase Function

Published on: May 14, 2021

Drosophila von Hippel-Lindau tumor suppressor complex possesses E3 ubiquitin ligase activity

T Aso1, K Yamazaki, T Aigaki

  • 1Department of Viral Oncology, Cancer Institute, Japanese Foundation for Cancer Research, 1-37-1 Kami-ikebukuro, Toshima-ku, Tokyo, 170-8455, Japan. taso@jfcr.or.jp

Biochemical and Biophysical Research Communications
|September 28, 2000
PubMed

Insights

The von Hippel-Lindau (VHL) gene

Area of Science:

  • Molecular Biology
  • Genetics
  • Cancer Research

Background:

  • Mutations in the von Hippel-Lindau (VHL) tumor suppressor gene are linked to various human cancers, including renal cell carcinoma and pheochromocytoma.
  • The VHL protein plays a critical role in cellular regulation and tumor suppression.

Purpose of the Study:

  • To identify and characterize the Drosophila homolog of the VHL gene.
  • To investigate the functional conservation of VHL protein in a model organism.

Main Methods:

  • Bioinformatic analysis to identify the Drosophila VHL homolog.
  • Biochemical assays to study protein interactions and enzymatic activity.
  • Ubiquitination assays to identify protein targets.

Main Results:

  • The Drosophila VHL protein shares significant sequence similarity with human VHL.
  • Drosophila VHL forms a complex with Elongins B/C, Cul-2, and Rbx1, exhibiting E3 ubiquitin ligase activity.
  • Hypoxia-inducible factor (HIF)-1alpha is identified as a ubiquitination target for both human and Drosophila VHL complexes.

Conclusions:

  • The functional conservation of VHL and its associated complex in Drosophila provides a valuable model for studying VHL-related diseases.
  • The findings highlight the conserved role of VHL in regulating hypoxia-inducible factors across species.

More Related Videos

Functional Characterization of RING-Type E3 Ubiquitin Ligases In Vitro and In Planta10:27

Functional Characterization of RING-Type E3 Ubiquitin Ligases In Vitro and In Planta

Published on: December 5, 2019

Identifying Protein-protein Interaction in Drosophila Adult Heads by Tandem Affinity Purification (TAP)10:36

Identifying Protein-protein Interaction in Drosophila Adult Heads by Tandem Affinity Purification (TAP)

Published on: December 5, 2013

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...
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...
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 daughter...
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...
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.
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 activation may...