The ubiquitin ligase Nedd4-1 is dispensable for the regulation of PTEN stability and localization
2008 | journal article; research paper. A publication with affiliation to the University of Göttingen.
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The ubiquitin ligase Nedd4-1 is dispensable for the regulation of PTEN stability and localization
Fouladkou, F.; Landry, T.; Kawabe, H.; Neeb, A.; Lu, C.; Brose, N. & Stambolic, V. et al. (2008)
Proceedings of the National Academy of Sciences, 105(25) pp. 8585-8590. DOI: https://doi.org/10.1073/pnas.0803233105
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- Authors
- Fouladkou, Fatemeh; Landry, Tamara; Kawabe, Hiroshi; Neeb, Antje; Lu, Chen; Brose, Nils ; Stambolic, Vuk; Rotin, Daniela
- Abstract
- PTEN is a tumor suppressor frequently mutated in cancer. Recent reports implicated Nedd4-1 as the E3 ubiquitin ligase for PTEN that regulates its stability and nuclear localization. We tested the physiological role of Nedd4-1 as a PTEN regulator by using cells and tissues derived from two independently generated strains of mice with their Nedd4-1 gene disrupted. PTEN stability and ubiquitination were indistinguishable between the wild-type and Nedd4-1-deficient cells, and an interaction between the two proteins could not be detected. Moreover, PTEN subcellular distribution, showing prominent cytoplasmic and nuclear staining, was independent of Nedd4-1 presence. Finally, activation of PKB/Akt, a major downstream target of cytoplasmic PTEN activity, and the ability of PTEN to transactivate the Rad51 promoter, a measure of its nuclear function, were unaffected by the loss of Nedd4-1. Taken together, our results fail to support a role for Nedd4-1 as the E3 ligase regulating PTEN stability and subcellular localization.
- Issue Date
- 2008
- Publisher
- Natl Acad Sciences
- Journal
- Proceedings of the National Academy of Sciences
- ISSN
- 0027-8424