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Severe Acute Respiratory Syndrome-associated Coronavirus Nucleocapsid Protein Interacts with Smad3 and Modulates Transforming Growth Factor-β Signaling
Open accessAbstract
Severe acute respiratory syndrome (SARS) is an acute infectious disease with significant mortality. A typical clinical feature associated with SARS is pulmonary fibrosis and the associated lung failure. However, the underlying mechanism remains elusive. In this study, we demonstrate that SARS-associated coronavirus (SARS-CoV) nucleocapsid (N) protein potentiates transforming growth factor-beta (TGF-beta)-induced expression of plasminogen activator inhibitor-1 but attenuates Smad3/Smad4-mediated apoptosis of human peripheral lung epithelial HPL1 cells. The promoting effect of N protein on the transcriptional responses of TGF-beta is Smad3-specific. N protein associates with Smad3 and promotes Smad3-p300 complex formation while it interferes with the complex formation between Smad3 and Smad4. These findings provide evidence of a novel mechanism whereby N protein modulates TGF-beta signaling to block apoptosis of SARS-CoV-infected host cells and meanwhile promote tissue fibrosis. Our results reveal a novel mode of Smad3 action in a Smad4-independent manner and may lead to successful strategies for SARS treatment by targeting the TGF-beta signaling molecules.
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Citations
Cites
SPECIFICITY AND VERSATILITY IN TGF-β SIGNALING THROUGH SMADS
Feng, X.-H., & Derynck, R. (2005) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.21.022404.142018 · Cited by 1,869
Cited by
Coronaviruses post-SARS: update on replication and pathogenesis
Perlman, S., & Netland, J. (2009) · Nature Reviews Microbiology · doi:10.1038/nrmicro2147 · Cited by 1,764
SARS‐coronavirus modulation of myocardial ACE2 expression and inflammation in patients with SARS
Oudit, G. Y., Kassiri, Z., Jiang, C., Liu, P. P., Poutanen, S. M., Penninger, J. M., & Butany, J. (2009) · European Journal of Clinical Investigation · doi:10.1111/j.1365-2362.2009.02153.x · Cited by 893
Ultra-High-Throughput Clinical Proteomics Reveals Classifiers of COVID-19 Infection
Messner, C. B., Demichev, V., Wendisch, D., Michalick, L., White, M., Freiwald, A., Textoris-Taube, K., Vernardis, S. I., Egger, A.-S., Kreidl, M., et al. (2020) · Cell Systems · doi:10.1016/j.cels.2020.05.012 · Cited by 561
Structural insights into SARS-CoV-2 proteins
Arya, R., Kumari, S., Pandey, B., Mistry, H., Bihani, S. C., Das, A., Prashar, V., Gupta, G. D., Panicker, L., & Kumar, M. (2021) · Journal of Molecular Biology · doi:10.1016/j.jmb.2020.11.024 · Cited by 348
Hanff, T. C., Mohareb, A. M., Giri, J., Cohen, J. B., & Chirinos, J. A. (2020) · American Journal of Hematology · doi:10.1002/ajh.25982 · Cited by 312
Metadata
- Authors
- Zhao, X., Nicholls, J. M., & Chen, Y.-G.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2008-02
- Volume
- 283
- Issue
- 6
- Pages
- 3272-3280
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2028305499
- Cited by
- 191
- References
- 1
- FWCI
- 2.16
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Zhao, X., Nicholls, J. M., & Chen, Y.-G. (2008). Severe Acute Respiratory Syndrome-associated Coronavirus Nucleocapsid Protein Interacts with Smad3 and Modulates Transforming Growth Factor-β Signaling. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.m708033200
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