HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

ESCRT proteins in physiology and disease.

Abstract
As a mechanism of signal attenuation, receptors for growth factors, peptide hormones and cytokines are internalized in response to ligand binding, followed by degradation in lysosomes. Receptor ubiquitination is a key signal for such downregulation, and four protein complexes known as endosomal sorting complex required for transport (ESCRT)-0, -I, -II and -III have been identified as the machinery required for degradative endosomal sorting of ubiquitinated membrane proteins in yeast and metazoans. Three of these complexes contain ubiquitin-binding domains whereas ESCRT-III instead recruits deubiquitinating enzymes. The concerted action of the ESCRTs not only serves to sort ubiquitinated cargo but is also thought to cause inward vesiculation of endosomal membranes, thereby mediating biogenesis of multivesicular endosomes (MVEs). Because ligand-mediated receptor downregulation plays an important role in signal attenuation, it is not surprising that dysfunction of ESCRT components is associated with disease. In this review we discuss the possible roles of ESCRTs in protection against cancer, neurodegenerative diseases and bacterial infections, and we highlight the fact that many RNA viruses exploit the ESCRT machinery for the final abscission step of their budding from cells. We also review the additional functions of ESCRT proteins in cytokinesis and discuss how these may be related to ESCRT-associated pathologies.
AuthorsSusanne Stuffers, Andreas Brech, Harald Stenmark
JournalExperimental cell research (Exp Cell Res) Vol. 315 Issue 9 Pg. 1619-26 (May 15 2009) ISSN: 1090-2422 [Electronic] United States
PMID19013455 (Publication Type: Journal Article, Review)
Chemical References
  • Carrier Proteins
  • Multiprotein Complexes
  • Ubiquitin
  • Vesicular Transport Proteins
Topics
  • Animals
  • Carrier Proteins (metabolism)
  • Communicable Diseases (metabolism)
  • Endosomes (metabolism)
  • Humans
  • Multiprotein Complexes (metabolism)
  • Neoplasms (metabolism)
  • Neurodegenerative Diseases (metabolism)
  • Protein Transport (physiology)
  • Signal Transduction (physiology)
  • Ubiquitin (metabolism)
  • Vesicular Transport Proteins (metabolism)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: