The DOI matches its Crossref record; 36 of the 36 references it cites were found in a registry or an index.
The UbcH8 ubiquitin E2 enzyme is also the E2 enzyme for ISG15, an IFN-α/β-induced ubiquitin-like protein
Open accessAbstract
Ubiquitin-(Ub) like proteins (Ubls) are conjugated to their targets by an enzymatic cascade involving an E1 activating enzyme, an E2 conjugating enzyme, and in some cases an E3 ligase. ISG15 is a Ubl that is conjugated to cellular proteins after IFN-α/β stimulation. Although the E1 enzyme for ISG15 (Ube1L/E1 ISG15 ) has been identified, the identities of the downstream components of the ISG15 conjugation cascade have remained elusive. Here we report the purification of an E2 enzyme for ISG15 and demonstrate that it is UbcH8, an E2 that also functions in Ub conjugation. In vitro assays with purified Ub E2 enzymes and in vivo RNA interference assays indicate that UbcH8 is a major E2 enzyme for ISG15 conjugation. These results indicate that the ISG15 conjugation pathway overlaps or converges with the Ub conjugation pathway at the level of a specific E2 enzyme. Furthermore, these results raise the possibility that the ISG15 conjugation pathway might use UbcH8-competent Ub ligases in vivo . As an initial test of this hypothesis, we have shown that a UbcH8-competent Ub ligase conjugates ISG15 to a specific target in vitro . These results challenge the concept that Ub and Ubl conjugation pathways are strictly parallel and nonoverlapping and have important implications for understanding the regulation and function of ISG15 conjugation in the IFN-α/β response.
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Cites
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Cited by
Interferon-inducible antiviral effectors
Sadler, A. J., & Williams, B. R. G. (2008) · Nature Reviews Immunology · doi:10.1038/nri2314 · Cited by 2,160
ISG15 in antiviral immunity and beyond
Perng, Y.-C., & Lenschow, D. J. (2018) · Nature Reviews Microbiology · doi:10.1038/s41579-018-0020-5 · Cited by 855
E2 enzymes: more than just middle men
Stewart, M. D., Ritterhoff, T., Klevit, R. E., & Brzovic, P. S. (2016) · Cell Research · doi:10.1038/cr.2016.35 · Cited by 594
The family of ubiquitin‐conjugating enzymes (E2s): deciding between life and death of proteins
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An expanded arsenal of immune systems that protect bacteria from phages
Millman, A., Melamed, S., Leavitt, A., Doron, S., Bernheim, A., Hör, J., Garb, J., Bechon, N., Brandis, A., Lopatina, A., et al. (2022) · Cell Host & Microbe · doi:10.1016/j.chom.2022.09.017 · Cited by 428
Metadata
- Authors
- Zhao, C., Beaudenon, S. L., Kelley, M. L., Waddell, M. B., Yuan, W., Schulman, B. A., Huibregtse, J. M., & Krug, R. M.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2004-05-06
- Volume
- 101
- Issue
- 20
- Pages
- 7578-7582
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2072280896
- Cited by
- 329
- References
- 36
- FWCI
- 7.12
- Type
- journal article
- Language
- en
- Open access
- green
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- Zhao, C., Beaudenon, S. L., Kelley, M. L., Waddell, M. B., Yuan, W., Schulman, B. A., Huibregtse, J. M., & Krug, R. M. (2004). The UbcH8 ubiquitin E2 enzyme is also the E2 enzyme for ISG15, an IFN-α/β-induced ubiquitin-like protein. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.0402528101
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