The complex life of rhomboid pseudoproteases

Colin Adrain*, Miguel Cavadas

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

3 Citations (Scopus)
11 Downloads (Pure)

Abstract

Rhomboid pseudoproteases are catalytically inactive members of the rhomboid superfamily. The founding members, rhomboids, were first identified in Drosophila as serine intramembrane proteases that cleave transmembrane proteins, enabling signaling. This led to the discovery of the wider rhomboid superfamily, a clan that in metazoans is dominated by pseudoproteases. These so-called rhomboid pseudoproteases inherited from their catalytically active ancestors a conserved rhomboid-like domain and a propensity to regulate signaling. Lacking catalytic activity, they developed new ‘pseudoenzyme’ functions that include regulating the trafficking, turnover, and activity of their client proteins. Rhomboid pseudoproteases have preeminent roles in orchestrating immune cell activation, antiviral responses, and cytokine release in response to microbial infection, or in chronic diseases, and have also been implicated in growth factor signaling, cancer, and, more recently, metabolism. Here, we discuss the mechanism(s) of action of rhomboid pseudoproteases, contrasted with rhomboid proteases. We also highlight the roles of rhomboid pseudoproteases in mammalian physiology, which, quite paradoxically among pseudoenzymes, is understood much better than active rhomboids.

Original languageEnglish
Pages (from-to)4261-4283
Number of pages23
JournalFEBS journal
Volume287
Issue number19
DOIs
Publication statusPublished - 02 Oct 2020

Bibliographical note

Funding Information:
MC acknowledges support from FCT—Fundação para a Ciência e a Tecnologia (CEEC‐IND 2017). We apologize to all authors whose contributions could not be included due to space limitations. We are grateful for the ongoing support of our laboratory by Fundação Calouste Gulbenkian, Queen's University Belfast, and Fundação para a Ciência e Tecnologia (project LISBOA‐01‐0145–FEDER‐031330). The project leading to these results has received funding from ‘la Caixa’ Foundation (ID 100010434), under the agreement .

Funding Information:
MC acknowledges support from FCT?Funda??o para a Ci?ncia e a Tecnologia (CEEC-IND 2017). We apologize to all authors whose contributions could not be included due to space limitations. We are grateful for the ongoing support of our laboratory by Funda??o Calouste Gulbenkian, Queen's University Belfast, and Funda??o para a Ci?ncia e Tecnologia (project LISBOA-01-0145?FEDER-031330). The project leading to these results has received funding from ?la Caixa? Foundation (ID 100010434), under the agreement <LCF/PR/HR17/52150018>.

Publisher Copyright:
© 2020 The Authors. The FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies

Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.

Keywords

  • cancer
  • catalytically inactive enzyme homologs
  • endoplasmic reticulum-associated degradation
  • immunity
  • rhomboid pseudoproteases
  • signaling
  • trafficking control

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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