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| Status |
Public on Aug 29, 2019 |
| Title |
Kallikrein-mediated cytokeratin 10 degradation is required for VZV propagation in skin |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Varicella Zoster Virus (VZV) is a skin-tropic virus that infects epidermal keratinocytes and causes chickenpox. Although common, VZV infection can be life-threatening particularly in the immunocompromised. Therefore, understanding VZV-keratinocyte interactions is important to find new treatments beyond vaccination and anti-viral drugs. In VZV- infected skin, Kallikrein 6 (KLK6), and the ubiquitin-ligase MDM2 are up-regulated concomitant with Keratin 10 (K10) down-regulation. MDM2 binds to K10 targeting it for degradation via the ubiquitin-proteasome pathway. Preventing K10 degradation reduced VZV propagation in culture and prevented epidermal disruption in skin explants. K10 knockdown induced expression of the nuclear receptor subfamily 4, group A, member 1 (NR4A1) and enhanced viral propagation in culture. NR4A1 knockdown prevented viral propagation in culture, reduced LC3 levels and increased LAMP2 expression. We therefore describe a novel drug-able pathway whereby MDM2 ubiquitinates and degrades K10 increasing NR4A1 expression allowing VZV replication and propagation.
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| Overall design |
12 samples: 3 uninfected, 3 VZV infected, 3 VZV infected treated with Nutlin-3, 3 uninfected treated with nutlin-3. VZV infected samples were infected with the pOka strain of the VZV virus. Uninfected are the reference in this analysis.
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| Web link |
https://www.sciencedirect.com/science/article/pii/S0022202X19332385
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| Contributor(s) |
O'Shaughnessy R, Depledge D |
| Citation(s) |
31626786 |
| BioProject |
PRJNA561812 |
| |
| Submission date |
Aug 28, 2019 |
| Last update date |
Jan 14, 2020 |
| Contact name |
Ryan O'Shaughnessy |
| E-mail(s) |
[email protected]
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| Organization name |
Queen Mary University of London
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| Street address |
4 Newark Street
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| City |
London |
| ZIP/Postal code |
E12AT |
| Country |
United Kingdom |
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| Platforms (1) |
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| Samples (12)
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| Relations |
| SRA |
SRP219194 |
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