TY - JOUR
T1 - SMAD proteins
T2 - Mediators of diverse outcomes during infection
AU - Lai, Lachlan Yuek Shun
AU - Gracie, Nicholas Peter
AU - Gowripalan, Anjali
AU - Howell, Liam Michael
AU - Newsome, Timothy Peter
N1 - Publisher Copyright:
© 2022 The Authors
PY - 2022/4
Y1 - 2022/4
N2 - 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.
AB - 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.
KW - Cellular Signalling
KW - Infection
KW - Pathogen
KW - SMAD
KW - Transforming Growth Factor β
UR - http://www.scopus.com/inward/record.url?scp=85124232321&partnerID=8YFLogxK
U2 - 10.1016/j.ejcb.2022.151204
DO - 10.1016/j.ejcb.2022.151204
M3 - Review article
C2 - 35131661
AN - SCOPUS:85124232321
SN - 0171-9335
VL - 101
JO - European Journal of Cell Biology
JF - European Journal of Cell Biology
IS - 2
M1 - 151204
ER -