Abstract
A few small-molecule oxidants, most notably hydrogen peroxide, can act as messengers in signal transduction. They trigger so-called ‘thiol switches’, cysteine residues that are reversibly oxidized to transiently change the functional properties of their host proteins. The proteome-wide identification of functionally relevant ‘thiol switches’ is of significant interest. Unfortunately, prediction of redox-active cysteine residues on the basis of surface accessibility and other computational parameters appears to be of limited use. Proteomic thiol labeling approaches remain the most reliable strategy to discover new thiol switches in a hypothesis-free manner. We discuss if and how genomic knock-in strategies can help establish the physiological relevance of a ‘thiol switch’ on the organismal level. We conclude that surprisingly few attempts have been made to thoroughly verify the physiological relevance of thiol-based redox switches in mammalian model organisms.
Acknowledgments
We thank Bruce Morgan for his critical comments regarding the manuscript. We would like to acknowledge funding from the Deutsche Forschungsgemeinschaft under the priority program SPP 1710 (DFG Grants LE 2905/1-1 to L.I.L. and DI 731/3-1 to T.P.D.)
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©2015 by De Gruyter
Articles in the same Issue
- Frontmatter
- Guest Editorial
- Highlight: Dynamics of Thiol-Based Redox Switches
- Highlight: Dynamics of Thiol-based Redox Switches
- Incidence and physiological relevance of protein thiol switches
- Enzymatic control of cysteinyl thiol switches in proteins
- Thiol-based redox switches in prokaryotes
- Detection of thiol-based redox switch processes in parasites – facts and future
- Thiol switches in mitochondria: operation and physiological relevance
- Thiol switches in redox regulation of chloroplasts: balancing redox state, metabolism and oxidative stress
- Plant-specific CC-type glutaredoxins: functions in developmental processes and stress responses
- Redox imaging using genetically encoded redox indicators in zebrafish and mice
- Cytosolic thiol switches regulating basic cellular functions: GAPDH as an information hub?
- Redox diversity in ERAD-mediated protein retrotranslocation from the endoplasmic reticulum: a complex puzzle
- Redox regulation of T-cell receptor signaling
Articles in the same Issue
- Frontmatter
- Guest Editorial
- Highlight: Dynamics of Thiol-Based Redox Switches
- Highlight: Dynamics of Thiol-based Redox Switches
- Incidence and physiological relevance of protein thiol switches
- Enzymatic control of cysteinyl thiol switches in proteins
- Thiol-based redox switches in prokaryotes
- Detection of thiol-based redox switch processes in parasites – facts and future
- Thiol switches in mitochondria: operation and physiological relevance
- Thiol switches in redox regulation of chloroplasts: balancing redox state, metabolism and oxidative stress
- Plant-specific CC-type glutaredoxins: functions in developmental processes and stress responses
- Redox imaging using genetically encoded redox indicators in zebrafish and mice
- Cytosolic thiol switches regulating basic cellular functions: GAPDH as an information hub?
- Redox diversity in ERAD-mediated protein retrotranslocation from the endoplasmic reticulum: a complex puzzle
- Redox regulation of T-cell receptor signaling