| Autor: |
Shruti Apte, Smita Bhutda, Sourav Ghosh, Kuldeep Sharma, Thomas E. Barton, Soham Dibyachintan, Osheen Sahay, Suvapriya Roy, Akash Raj Sinha, Harikrishna Adicherla, Jyotirmoy Rakshit, Shiying Tang, Akshay Datey, Shweta Santra, Jincy Joseph, Sreeja Sasidharan, Sven Hammerschmidt, Dipshikha Chakravortty, Marco R. Oggioni, Manas Kumar Santra, Daniel R. Neill, Anirban Banerjee |
| Rok vydání: |
2023 |
| Předmět: |
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| Zdroj: |
Science Advances. 9 |
| ISSN: |
2375-2548 |
| DOI: |
10.1126/sciadv.ade1851 |
| Popis: |
Sensing of pathogens by ubiquitination is a critical arm of cellular immunity. However, universal ubiquitination targets on microbes remain unidentified. Here, using in vitro, ex vivo, and in vivo studies, we identify the first protein-based ubiquitination substrates on phylogenetically diverse bacteria by unveiling a strategy that uses recognition of degron-like motifs. Such motifs form a new class of intra-cytosolic pathogen-associated molecular patterns (PAMPs). Their incorporation enabled recognition of nonubiquitin targets by host ubiquitin ligases. We find that SCF FBW7 E3 ligase, supported by the regulatory kinase, glycogen synthase kinase 3β, is crucial for effective pathogen detection and clearance. This provides a mechanistic explanation for enhanced risk of infections in patients with chronic lymphocytic leukemia bearing mutations in F-box and WD repeat domain containing 7 protein. We conclude that exploitation of this generic pathogen sensing strategy allows conservation of host resources and boosts antimicrobial immunity. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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