TY - JOUR
T1 - Rhomboid proteins
T2 - Conserved membrane proteases with divergent biological functions
AU - Urban, Sinisa
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2006/11/15
Y1 - 2006/11/15
N2 - The rhomboid gene was discovered in Drosophila, where it encodes a seven transmembrane protein that is the signal-generating component of epidermal growth factor (EGF) receptor signaling during development. Although metazoan developmental regulators are rarely conserved outside the animal kingdom, rhomboid proteins are conserved in all kingdoms of life, but the significance of this remains unclear. Recent biochemical reconstitution and high-resolution crystal structures have provided proof that rhomboid proteins function as novel intramembrane proteases, with a serine protease-like catalytic apparatus embedded within the membrane bilayer, buried in a hydrophilic cavity formed by a protein ring. A thorough consideration of all known examples of rhomboid function suggests that, despite biochemical similarity in mechanism and specificity, rhomboid proteins function in diverse processes including quorum sensing in bacteria, mitochondrial membrane fusion, apoptosis, and stem cell differentiation in eukaryotes; rhomboid proteins are also now starting to be linked to human disease, including early-onset blindness, diabetes, and parasitic diseases. Regulating cell signaling is at the heart of rhomboid protein function in many, but not all, of these processes. Further study of these novel enzymes promises to reveal the evolutionary path of rhomboid protein function, which could provide insights into the forces that drive the molecular evolution of regulatory mechanisms.
AB - The rhomboid gene was discovered in Drosophila, where it encodes a seven transmembrane protein that is the signal-generating component of epidermal growth factor (EGF) receptor signaling during development. Although metazoan developmental regulators are rarely conserved outside the animal kingdom, rhomboid proteins are conserved in all kingdoms of life, but the significance of this remains unclear. Recent biochemical reconstitution and high-resolution crystal structures have provided proof that rhomboid proteins function as novel intramembrane proteases, with a serine protease-like catalytic apparatus embedded within the membrane bilayer, buried in a hydrophilic cavity formed by a protein ring. A thorough consideration of all known examples of rhomboid function suggests that, despite biochemical similarity in mechanism and specificity, rhomboid proteins function in diverse processes including quorum sensing in bacteria, mitochondrial membrane fusion, apoptosis, and stem cell differentiation in eukaryotes; rhomboid proteins are also now starting to be linked to human disease, including early-onset blindness, diabetes, and parasitic diseases. Regulating cell signaling is at the heart of rhomboid protein function in many, but not all, of these processes. Further study of these novel enzymes promises to reveal the evolutionary path of rhomboid protein function, which could provide insights into the forces that drive the molecular evolution of regulatory mechanisms.
KW - Cell signalling
KW - Malaria
KW - Plasmodium
KW - Presenilin
KW - Regulated intramembrane proteolysis
KW - Toxoplasma
UR - http://www.scopus.com/inward/record.url?scp=33751246749&partnerID=8YFLogxK
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U2 - 10.1101/gad.1488606
DO - 10.1101/gad.1488606
M3 - Review article
C2 - 17114579
AN - SCOPUS:33751246749
VL - 20
SP - 3054
EP - 3068
JO - Genes and Development
JF - Genes and Development
SN - 0890-9369
IS - 22
ER -