The DOI matches its Crossref record; 8 of the 8 references it cites were found in a registry or an index.
Fbxw7α- and GSK3-mediated degradation of p100 is a pro-survival mechanism in multiple myeloma
Open accessAbstract
Fbxw7α is a member of the F-box family of proteins, which function as the substrate-targeting subunits of SCF (Skp1/Cul1/F-box protein) ubiquitin ligase complexes. Using differential purifications and mass spectrometry, we identified p100, an inhibitor of NF-κB signalling, as an interactor of Fbxw7α. p100 is constitutively targeted in the nucleus for proteasomal degradation by Fbxw7α, which recognizes a conserved motif phosphorylated by GSK3. Efficient activation of non-canonical NF-κB signalling is dependent on the elimination of nuclear p100 through either degradation by Fbxw7α or exclusion by a newly identified nuclear export signal in the carboxy terminus of p100. Expression of a stable p100 mutant, expression of a constitutively nuclear p100 mutant, Fbxw7α silencing or inhibition of GSK3 in multiple myeloma cells with constitutive non-canonical NF-κB activity results in apoptosis both in cell systems and xenotransplant models. Thus, in multiple myeloma, Fbxw7α and GSK3 function as pro-survival factors through the control of p100 degradation.
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Cites
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The SCF ubiquitin ligase: insights into a molecular machine
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Self-citationWelcker, M., & Clurman, B. E. (2008) · Nature Reviews Cancer · doi:10.1038/nrc2290 · Cited by 1,084
Promiscuous Mutations Activate the Noncanonical NF-κB Pathway in Multiple Myeloma
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Degradation of Cdc25A by β-TrCP during S phase and in response to DNA damage
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NF‐κB signaling in inflammation and cancer
Zhang, T., Ma, C., Zhang, Z., Zhang, H., & Hu, H. (2021) · MedComm · doi:10.1002/mco2.104 · Cited by 574
Ubiquitin ligases in oncogenic transformation and cancer therapy
Senft, D., Qi, J., & Ronai, Z. A. (2018) · Nature Reviews Cancer · doi:10.1038/nrc.2017.105 · Cited by 489
Tumor suppression by the Fbw7 ubiquitin ligase: mechanisms and opportunities
Davis, R. J., Welcker, M., & Clurman, B. E. (2014) · Cancer Cell · doi:10.1016/j.ccell.2014.09.013 · Cited by 343
Regulation of Pluripotency and Cellular Reprogramming by the Ubiquitin-Proteasome System
Buckley, S. M., Aranda-Orgilles, B., Strikoudis, A., Apostolou, E., Loizou, E., Moran-Crusio, K., Farnsworth, C. L., Koller, A. A., Dasgupta, R., Silva, J. C., et al. (2012) · Cell Stem Cell · doi:10.1016/j.stem.2012.09.011 · Cited by 272
Proteomic screen reveals Fbw7 as a modulator of the NF-κB pathway
Arabi, A., Ullah, K., Branca, R. M. M., Johansson, J., Bandarra, D., Haneklaus, M., Fu, J., Ariës, I., Nilsson, P., Den Boer, M. L., et al. (2012) · Nature Communications · doi:10.1038/ncomms1975 · Cited by 90
Metadata
- Authors
- Busino, L., Millman, S. E., Scotto, L., Kyratsous, C. A., Basrur, V., O’Connor, O., Hoffmann, A., Elenitoba-Johnson, K. S., & Pagano, M.
- Venue
- Nature Cell Biology
- Published
- 2012-03-04
- Volume
- 14
- Issue
- 4
- Pages
- 375-385
- ISSN
- 1465-7392 (ISSN-L)
- 1476-4679
- OpenAlex
- W2093075930
- Cited by
- 167
- References
- 8
- FWCI
- 5.75
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Busino, L., Millman, S. E., Scotto, L., Kyratsous, C. A., Basrur, V., O’Connor, O., Hoffmann, A., Elenitoba-Johnson, K. S., & Pagano, M. (2012). Fbxw7α- and GSK3-mediated degradation of p100 is a pro-survival mechanism in multiple myeloma. Nature Cell Biology. https://doi.org/10.1038/ncb2463
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