The DOI matches its Crossref record; 2 of the 2 references it cites were found in a registry or an index.
Skp2 inhibits FOXO1 in tumor suppression through ubiquitin-mediated degradation
Open accessAbstract
Forkhead transcription factors FOXO1 (FKHR), FOXO3a (FKHRL1), and FOXO4 (AFX) play a pivotal role in tumor suppression by inducing growth arrest and apoptosis. Loss of function of these factors due to phosphorylation and proteasomal degradation has been implicated in cell transformation and malignancy. However, the ubiquitin ligase necessary for the ubiquitination of the FOXO factors and the relevance of this regulation to tumorigenesis have not been characterized. Here we demonstrate that Skp2, an oncogenic subunit of the Skp1/Cul1/F-box protein ubiquitin complex, interacts with, ubiquitinates, and promotes the degradation of FOXO1. This effect of Skp2 requires Akt-specific phosphorylation of FOXO1 at Ser-256. Moreover, expression of Skp2 inhibits transactivation of FOXO1 and abolishes the inhibitory effect of FOXO1 on cell proliferation and survival. Furthermore, expression of the FOXO1 protein is lost in a mouse lymphoma model, where Skp2 is overexpressed. These data suggest that the Skp2-promoted proteolysis of FOXO1 plays a key role in tumorigenesis.
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Cites
(2004) · doi:10.1016/s0092-8674(04)00452-0 · Cited by 1,356
IκB Kinase Promotes Tumorigenesis through Inhibition of Forkhead FOXO3a
Hu, M. C.-T., Lee, D.-F., Xia, W., Golfman, L. S., Ou-Yang, F., Yang, J.-Y., Zou, Y., Bao, S., Hanada, N., Saso, H., et al. (2004) · Cell · doi:10.1016/s0092-8674(04)00302-2 · Cited by 868
Cited by
FOXO transcription factors at the interface between longevity and tumor suppression
Greer, E. L., & Brunet, A. (2005) · Oncogene · doi:10.1038/sj.onc.1209086 · Cited by 1,310
Autophagy in malignant transformation and cancer progression
Galluzzi, L., Pietrocola, F., Bravo‐San Pedro, J. M., Amaravadi, R. K., Baehrecke, E. H., Cecconi, F., Codogno, P., Debnath, J., Gewirtz, D. A., Karantza, V., et al. (2015) · The EMBO Journal · doi:10.15252/embj.201490784 · Cited by 1,182
Calnan, D. R., & Brunet, A. (2008) · Oncogene · doi:10.1038/onc.2008.21 · Cited by 1,170
Dynamic FoxO transcription factors
Huang, H., & Tindall, D. J. (2007) · Journal of Cell Science · doi:10.1242/jcs.001222 · Cited by 1,113
Self-citationDeregulated proteolysis by the F-box proteins SKP2 and β-TrCP: tipping the scales of cancer
Frescas, D., & Pagano, M. (2008) · Nature Reviews Cancer · doi:10.1038/nrc2396 · Cited by 890
Metadata
- Authors
- Huang, H., Regan, K. M., Wang, F., Wang, D., Smith, D. I., van Deursen, J. M. A., & Tindall, D. J.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2005-01-24
- Volume
- 102
- Issue
- 5
- Pages
- 1649-1654
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2056383938
- Cited by
- 518
- References
- 2
- FWCI
- 10.72
- Type
- journal article
- Language
- en
- Open access
- green
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