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BTB Domain-containing Speckle-type POZ Protein (SPOP) Serves as an Adaptor of Daxx for Ubiquitination by Cul3-based Ubiquitin Ligase
Open accessAbstract
Daxx is a multifunctional protein that regulates a variety of cellular processes, including transcription, cell cycle, and apoptosis. SPOP is a BTB (Bric-a-brac/Tramtrack/Broad complex) protein that constitutes Cul3-based ubiquitin ligases. Here we show that SPOP serves as an adaptor of Daxx for the ubiquitination by Cul3-based ubiquitin ligase and subsequent degradation by the proteasome. Expression of SPOP with Cul3 markedly reduced Daxx level, and this degradation was blocked by SPOP-specific short hairpin RNAs. Inhibition of the proteasome by MG132 caused the prevention of Daxx degradation in parallel with the accumulation of ubiquitinated Daxx. Expression of SPOP with Cul3 reversed Daxx-mediated repression of ETS1- and p53-dependent transcription, and short hairpin RNA-mediated knock down of SPOP blocked the recovery of their transcriptional activation. Furthermore, Daxx degradation led to the cleavage of poly(ADP-ribose) polymerase and the increase in the number of terminal deoxynucleotidyltransferase-mediated dUTP-fluorescein nick end-labeling-positive apoptotic cells. These results suggest that SPOP/Cul3-ubiquitin ligase plays an essential role in the control of Daxx level and, thus, in the regulation of Daxx-mediated cellular processes, including transcriptional regulation and apoptosis.
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Cites
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Berger, M. F., Lawrence, M. S., Demichelis, F., Drier, Y., Cibulskis, K., Sivachenko, A. Y., Sboner, A., Esgueva, R., Pflueger, D., Sougnez, C., et al. (2011) · Nature · doi:10.1038/nature09744 · Cited by 1,234
The role of ubiquitination in tumorigenesis and targeted drug discovery
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Bouchard, J. J., Otero, J. H., Scott, D. C., Szulc, E., Martin, E. W., Sabri, N., Granata, D., Marzahn, M. R., Lindorff-Larsen, K., Salvatella, X., et al. (2018) · Molecular Cell · doi:10.1016/j.molcel.2018.08.027 · Cited by 391
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Metadata
- Authors
- Kwon, J. E., La, M., Oh, K. H., Oh, Y. M., Kim, G. R., Seol, J. H., Baek, S. H., Chiba, T., Tanaka, K., Bang, O. S., Joe, C. O., & Chung, C. H.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2006-05
- Volume
- 281
- Issue
- 18
- Pages
- 12664-12672
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1964605487
- Cited by
- 204
- References
- 5
- FWCI
- 3.68
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- CoChat. (2026). Citation check: BTB Domain-containing Speckle-type POZ Protein (SPOP) Serves as an Adaptor of Daxx for Ubiquitination by Cul3-based Ubiquitin Ligase. https://app.cochat.ai/papers/10.1074/jbc.m600204200
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- Kwon, J. E., La, M., Oh, K. H., Oh, Y. M., Kim, G. R., Seol, J. H., Baek, S. H., Chiba, T., Tanaka, K., Bang, O. S., Joe, C. O., & Chung, C. H. (2006). BTB Domain-containing Speckle-type POZ Protein (SPOP) Serves as an Adaptor of Daxx for Ubiquitination by Cul3-based Ubiquitin Ligase. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.m600204200
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