Publications by authors named "Iona Wallace"

Branched ubiquitin (Ub) chains constitute a sizable fraction of Ub polymers in human cells. Despite their abundance, our understanding of branched Ub function in cell signaling has been stunted by the absence of accessible methods and tools. Here we identify cellular branched-chain-specific binding proteins and devise approaches to probe K48-K63-branched Ub function.

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Article Synopsis
  • The study presents a detailed cryo-EM structure of a UBE1L-UBE2L6 complex bound to ISG15, highlighting the initial steps in recognizing ISG15 and recruiting UBE2L6.
  • It utilizes viral proteins from SARS-CoV-2 and influenza B to validate the significance of the ISG15 C-terminal region in the adenylation reaction.
  • The research also explores the interactions between UBE1L-ISG15 and UBE1L-UBE2L6, enabling the creation of mutants that affect important signalling pathways in the innate immune response.
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Type 1 interferon stimulation highly up-regulates all elements of a ubiquitin-like conjugation system that leads to ISGylation of target proteins. An ISG15-specific member of the deubiquitylase family, USP18, is up-regulated in a co-ordinated manner. USP18 can also provide a negative feedback by inhibiting JAK-STAT signalling through protein interactions independently of DUB activity.

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Cardiovascular toxicity is an important cause of drug failures in the later stages of drug development, early clinical safety assessment, and even postmarket withdrawals. Early-stage in vitro assessment of potential cardiovascular liabilities in the pharmaceutical industry involves assessment of interactions with cardiac ion channels, as well as induced pluripotent stem cell-derived cardiomyocyte-based functional assays, such as calcium flux and multielectrode-array assays. These methods are appropriate for the identification of acute functional cardiotoxicity but structural cardiotoxicity, which manifests effects after chronic exposure, is often only captured in vivo.

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