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

Cancer Cell. 2008 Jul 8;14(1):10-21. doi: 10.1016/j.ccr.2008.06.001.

Abstract

The involvement of the homologous to E6-AP carboxyl terminus (HECT)-type E3s in crucial signaling pathways implicated in tumorigenesis is presently an area of intense research and extensive scientific interest. This review highlights recent discoveries on the ubiquitin-mediated degradation of crucial tumor suppressor molecules catalyzed by the HECT-type E3s. By providing a portrait of their protein targets, we intend to link the substrate specificity of HECT-type E3s with their contribution to tumorigenesis. Moreover, we discuss the relevance of targeting the HECT E3s, through the development of small-molecule inhibitors, as an anticancer therapeutic strategy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Cell Transformation, Neoplastic / genetics
  • Cell Transformation, Neoplastic / metabolism*
  • Endosomal Sorting Complexes Required for Transport
  • Enzyme Inhibitors / pharmacology
  • Gene Expression Regulation, Enzymologic
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Nedd4 Ubiquitin Protein Ligases
  • Neoplasms / drug therapy
  • Neoplasms / enzymology*
  • Neoplasms / genetics
  • Repressor Proteins / metabolism
  • Signal Transduction* / drug effects
  • Signal Transduction* / genetics
  • Substrate Specificity
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism*
  • Ubiquitin / metabolism*
  • Ubiquitin-Protein Ligases / antagonists & inhibitors
  • Ubiquitin-Protein Ligases / genetics
  • Ubiquitin-Protein Ligases / metabolism*

Substances

  • Antineoplastic Agents
  • Endosomal Sorting Complexes Required for Transport
  • Enzyme Inhibitors
  • Repressor Proteins
  • Tumor Suppressor Proteins
  • Ubiquitin
  • HUWE1 protein, human
  • ITCH protein, human
  • Nedd4 Ubiquitin Protein Ligases
  • UBE3A protein, human
  • WWP1 protein, human
  • Ubiquitin-Protein Ligases