HECT E3s and human disease

Martin Scheffner,Olivier Staub

doi:10.1186/1471-2091-8-s1-s6

Abstract

In a simplified view, members of the HECT E3 family have a modular structure consisting of the C-terminal HECT domain, which is catalytically involved in the attachment of ubiquitin to substrate proteins, and N-terminal extensions of variable length and sequence that mediate the substrate specificity of the respective HECT E3. Although the physiologically relevant substrates of most HECT E3s have remained elusive, it is becoming increasingly clear that HECT E3s play an important role in sporadic and hereditary human diseases including cancer, cardiovascular (Liddle's syndrome) and neurological (Angelman syndrome) disorders, and/or in disease-relevant processes including bone homeostasis, immune response and retroviral budding. Thus, molecular approaches to target the activity of distinct HECT E3s, regulators thereof, and/or of HECT E3 substrates could prove valuable in the treatment of the respective diseases.Publication history: Republished from Current BioData's Targeted Proteins database (TPdb; ).

Highlights

HECT E3 ubiquitin-protein ligases have been found from yeast to humans and range in size from approximately 80 kDa to more than 500 kDa
While the HECT domain represents the catalytic domain of HECT E3s [1,2,3], the substrate specificity of these proteins is assumed to be determined by their respective Nterminal extensions
Based on the presence of distinct amino acid sequence motifs within these N-terminal extensions, human HECT E3s can be grouped into three subfamilies: HECT E3s with RLDs (RCC1-like domains) (which are termed HERC (HECT and RCC1-like domain) E3s) [10], HECT E3s with WW domains [11,12] and HECT E3s that neither contain RLDs nor WW domains (termed SI(ngle)HECT E3s)

Summary

Introduction

HECT E3 ubiquitin-protein ligases have been found from yeast to humans and range in size from approximately 80 kDa to more than 500 kDa. HERC1 was reported to interact with TSC2, a GTPase-activating protein of the Rheb GTPase, in murine and human cells, and to target it for degradation [21].

Results

Conclusion