SMAD proteins: Mediators of diverse outcomes during infection

Lachlan Yuek Shun Lai, Nicholas Peter Gracie, Anjali Gowripalan, Liam Michael Howell, Timothy Peter Newsome*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

19 Citations (Scopus)

Abstract

Understanding the relationship between host and pathogen is key to combatting disease. SMAD transcription factors, which transmit TGF-β superfamily signalling, mediate an array of outcomes during embryogenesis, inflammation, cancer, and immunity. Surprisingly, these activities can sometimes be directly opposed; for example, SMAD3 has been reported as tumour suppressor by arresting cell cycle progression but conversely promotes cancer metastasis. A growing body of literature has identified SMADs as prominent targets during viral and bacterial infection for modulating host signalling. During infection, the activity of SMAD-containing transcriptional complexes can be finely tuned by pathogens to enhance infectivity and spread. SMAD signalling can be modulated at many levels, such as upstream at the ligand and receptor, or by direct interactions with SMADs. These alterations can increase pathogen dissemination, induce fibrosis, over-activate, or attenuate the host immune response. Here, we summarise the diverse mechanisms by which pathogens have evolved to sway SMAD signalling in their favour. Understanding the intricacies of host–pathogen interactions through this lens may elucidate aspects of SMAD function in cancer development, homoeostasis, and immune signalling previously overlooked. These insights are an opportunity to identify novel TGF-β or BMP-targeted therapeutics for applications to infectious disease contexts.

Original languageEnglish
Article number151204
JournalEuropean Journal of Cell Biology
Volume101
Issue number2
DOIs
Publication statusPublished - Apr 2022
Externally publishedYes

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