SMAD proteins: Mediators of diverse outcomes during infection
Lachlan Yuek Shun Lai1, Nicholas Peter Gracie1, Anjali Gowripalan2
1School of Life and Environmental Sciences, The University of Sydney, Sydney, New South Wales, Australia.
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.
Insights
Pathogens manipulate SMAD signaling pathways, crucial for immunity and development, to enhance infection and spread. Understanding these host-pathogen interactions can reveal new therapeutic targets for infectious diseases.
Area of Science:
- Molecular Biology
- Immunology
- Cell Biology
Background:
- SMAD transcription factors are key mediators of TGF-β superfamily signaling, influencing critical processes like development, immunity, and cancer.
- SMAD proteins play complex roles in disease, with SMAD3 acting as both a tumor suppressor and a promoter of metastasis.
- Pathogens exploit host SMAD signaling to manipulate cellular processes and promote infection.
Purpose of the Study:
- To summarize the diverse mechanisms pathogens use to modulate SMAD signaling.
- To highlight the intricate interplay between host SMADs and pathogens during infection.
- To explore the potential of targeting SMAD signaling for novel infectious disease therapeutics.
Main Methods:
- Literature review of studies on SMAD signaling and host-pathogen interactions.
- Analysis of mechanisms by which pathogens target SMADs at various signaling levels.
- Synthesis of findings to elucidate SMADs' role in infection and disease.
Main Results:
- Pathogens finely tune SMAD-containing transcriptional complexes to enhance infectivity and spread.
- SMAD signaling modulation by pathogens can lead to increased dissemination, fibrosis, and altered immune responses.
- Pathogens interact with SMADs directly or modulate upstream signaling components.
Conclusions:
- Understanding pathogen manipulation of SMAD signaling offers insights into SMAD functions in cancer, homeostasis, and immunity.
- Targeting TGF-β or BMP pathways offers a potential therapeutic strategy for infectious diseases.
- Elucidating these host-pathogen interactions can uncover previously overlooked aspects of SMAD signaling.
More Related Videos
Related Concept Videos
01:20The JAK-STAT Signaling Pathway
01:16TGF - β Signaling Pathway
01:23Antimicrobial Proteins
Interferons
Interferons (IFNs) are proteins produced by lymphocytes, macrophages, and fibroblasts infected with viruses. While IFNs cannot prevent viruses from entering and...
01:19Interactions Between Signaling Pathways
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
01:17Intracellular Signaling Affects Focal Adhesions
Some...
01:28Inflammatory Response
Inflammation can be triggered by various stimuli, such as impact, abrasion, chemical irritation, infections, and extreme hot or cold temperatures. These can damage cells and connective tissue fibers,...