The HECT family of E3 ubiquitin ligases: multiple players in cancer development

Related Experiment Video

Updated: Jul 3, 2026

In Vitro Analysis of E3 Ubiquitin Ligase Function
06:06

In Vitro Analysis of E3 Ubiquitin Ligase Function

Published on: May 14, 2021

Francesca Bernassola1, Michael Karin, Aaron Ciechanover

  • 1Department of Experimental Medicine and Biochemical Sciences, Biochemistry IDI-IRCCS Laboratory, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, Italy.

Cancer Cell
|July 5, 2008
PubMed

Insights

Homologous to E6-AP carboxyl terminus (HECT)-type E3 ligases target tumor suppressors for degradation, influencing cancer development. Inhibiting these E3 ligases offers a promising anticancer therapeutic strategy.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Oncology

Background:

  • Homologous to E6-AP carboxyl terminus (HECT)-type E3 ubiquitin ligases are critical regulators of cellular processes.
  • Their dysregulation is increasingly linked to various human cancers, highlighting their role in tumorigenesis.
  • Understanding HECT E3 ligase function is crucial for developing targeted cancer therapies.

Purpose of the Study:

  • To review recent advances in the understanding of HECT-type E3 ligases.
  • To elucidate the role of HECT-type E3s in the ubiquitin-mediated degradation of tumor suppressor proteins.
  • To explore the therapeutic potential of targeting HECT-type E3s in cancer treatment.

Main Methods:

  • Literature review of recent scientific discoveries.
  • Analysis of protein targets and substrate specificity of HECT-type E3s.
  • Discussion of small-molecule inhibitors targeting HECT E3 ligases.

Main Results:

  • HECT-type E3s catalyze the degradation of key tumor suppressor molecules.
  • The substrate specificity of HECT-type E3s is directly linked to their involvement in tumorigenesis.
  • Small-molecule inhibitors targeting HECT E3s demonstrate potential as anticancer agents.

Conclusions:

  • HECT-type E3 ligases play a significant role in cancer by degrading tumor suppressors.
  • Targeting HECT E3 ligases represents a viable strategy for novel anticancer therapies.
  • Further research into HECT E3 ligase inhibitors is warranted for clinical translation.

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

A Scalable, Cell-Based Method for the Functional Assessment of Ube3a Variants06:35

A Scalable, Cell-Based Method for the Functional Assessment of Ube3a Variants

Published on: October 10, 2022

Related Concept Videos

Hedgehog Signaling Pathway02:33

Hedgehog Signaling Pathway

The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
Cadherins in Tissue Organization01:19

Cadherins in Tissue Organization

The cadherins are a superfamily of cell adhesion molecules comprising over 180 variants, with specific tissues expressing a particular combination of cadherin types. Cadherins generally exhibit homophilic binding; i.e., cadherins on one cell bind to cadherins of the same or closely related type on another cell. Thus, cells of the same type have a specific affinity to bind to each other and sort themselves into clusters to form tissues.
Cell Sorting During Development
Cell sorting plays an...
Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal01:22

Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal

Erythropoietin-producing hepatocellular carcinoma receptor (Eph) and its ligand, Eph receptor-interacting protein (Ephrin) were first discovered in the human carcinoma cell line, hence the name. Ephrin-Eph interaction guides cells to reach their appropriate location in adult tissues. They also play an essential role in the immune system by helping in immune cell migration, adhesion, and activation. Based on their structure and function, Eph is divided into two classes — EphA and EphB.
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.