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Dysregulation of protein modification by ISG15 results in brain cell injury
Open accessAbstract
UBP43 (USP18) is a protease that removes the ubiquitin-like modifier ISG15 from conjugated proteins. Here we present the first report of dysregulation of protein ISG15 modification by the generation of UBP43 knockout mice. In the absence of UBP43, brain tissue showed an elevated level of ISG15 conjugates, and cellular necrosis was evident in the ependyma. Such disruption of the blood–brain barrier resulted in severe neurologic disorders. These results demonstrate that UBP43 plays a critical role in maintaining the homeostatic balance of ISG15-conjugated protein, and that regulation of cellular levels of ISG15 protein modification is essential for brain cell function.
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Nijman, S. M. B., Luna-Vargas, M. P. A., Velds, A., Brummelkamp, T. R., Dirac, A. M. G., Sixma, T. K., & Bernards, R. (2005) · Cell · doi:10.1016/j.cell.2005.11.007 · Cited by 1,854
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Positive Regulation of Interferon Regulatory Factor 3 Activation by Herc5 via ISG15 Modification
Shi, H.-X., Yang, K., Liu, X., Liu, X.-Y., Wei, B., Shan, Y.-F., Zhu, L.-H., & Wang, C. (2010) · Molecular and Cellular Biology · doi:10.1128/mcb.01466-09 · Cited by 266
Metadata
- Authors
- Ritchie, K. J., Malakhov, M. P., Hetherington, C. J., Zhou, L., Little, M.-T., Malakhova, O. A., Sipe, J. C., Orkin, S. H., & Zhang, D.-E.
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2002-09-01
- Volume
- 16
- Issue
- 17
- Pages
- 2207-2212
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- OpenAlex
- W2120611983
- Cited by
- 159
- References
- 0
- Type
- posted content
- Language
- en
- Open access
- diamond
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- Ritchie, K. J., Malakhov, M. P., Hetherington, C. J., Zhou, L., Little, M.-T., Malakhova, O. A., Sipe, J. C., Orkin, S. H., & Zhang, D.-E. (2002). Dysregulation of protein modification by ISG15 results in brain cell injury. Genes & Development. https://doi.org/10.1101/gad.1010202
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