Inactive rhomboid proteins: New mechanisms with implications in health and disease

Marius K Lemberg, Colin Adrain

Research output: Contribution to journalReview article

20 Citations (Scopus)

Abstract

Rhomboids, proteases containing an unusual membrane-integral serine protease active site, were first identified in Drosophila, where they fulfill an essential role in epidermal growth factor receptor signaling, by cleaving membrane-tethered growth factor precursors. It has recently become apparent that eukaryotic genomes harbor conserved catalytically inactive rhomboid protease homologs, including derlins and iRhoms. Here we highlight how loss of proteolytic activity was followed in evolution by impressive functional diversification, enabling these pseudoproteases to fulfill crucial roles within the secretory pathway, including protein degradation, trafficking regulation, and inflammatory signaling. We distil the current understanding of the roles of rhomboid pseudoproteases in development and disease. Finally, we address mechanistically how versatile features of proteolytically active rhomboids have been elaborated to serve the sophisticated functions of their pseudoprotease cousins. By comparing functional and structural clues, we highlight common principles shared by the rhomboid superfamily, and make mechanistic predictions.

Original languageEnglish
Pages (from-to)29-37
Number of pages9
JournalSeminars in cell & developmental biology
Volume60
Early online date01 Jul 2016
DOIs
Publication statusPublished - 01 Dec 2016
Externally publishedYes

Bibliographical note

Copyright © 2016 Elsevier Ltd. All rights reserved.

Keywords

  • Animals
  • Disease
  • Health
  • Humans
  • Mitochondrial Proteins/metabolism
  • Models, Biological
  • Peptide Hydrolases/metabolism
  • Protein Transport

Fingerprint Dive into the research topics of 'Inactive rhomboid proteins: New mechanisms with implications in health and disease'. Together they form a unique fingerprint.

Cite this