Title |
Nontranscriptional Role of Hif-1α in Activation of γ-Secretase and Notch Signaling in Breast Cancer
|
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Published in |
Cell Reports, August 2014
|
DOI | 10.1016/j.celrep.2014.07.028 |
Pubmed ID | |
Authors |
Jennifer C. Villa, Danica Chiu, Alissa H. Brandes, Freddy E. Escorcia, Carlos H. Villa, William F. Maguire, Cheng-Jun Hu, Elisa de Stanchina, M. Celeste Simon, Sangram S. Sisodia, David A. Scheinberg, Yue-Ming Li |
Abstract |
γ-Secretase is composed of four proteins that are obligatory for protease activity: presenilin, nicastrin, Aph1, and Pen-2. Despite the progress toward understanding the function of these individual subunits, there is no information available pertaining to the modulation of γ-secretase in response to environmental changes in cells. Here, we show that hypoxia upregulates γ-secretase activity through a direct interaction with Hif-1α, revealing an unconventional function for Hif-1α as an enzyme subunit, which is distinct from its canonical role as a transcription factor. Moreover, hypoxia-induced cell invasion and metastasis are alleviated by either γ-secretase inhibitors or a dominant-negative Notch coactivator, indicating that γ-secretase/Notch signaling plays an essential role in controlling these cellular processes. The present study reveals a mechanism in which γ-secretase can achieve temporal control through conditional interactions with regulatory proteins, such as Hif-1α, under select physiological and pathological conditions. |
X Demographics
Geographical breakdown
Country | Count | As % |
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United States | 5 | 50% |
Australia | 1 | 10% |
Saudi Arabia | 1 | 10% |
Unknown | 3 | 30% |
Demographic breakdown
Type | Count | As % |
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Science communicators (journalists, bloggers, editors) | 2 | 20% |
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Mendeley readers
Geographical breakdown
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Spain | 1 | <1% |
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Demographic breakdown
Readers by professional status | Count | As % |
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Student > Master | 15 | 14% |
Student > Bachelor | 13 | 12% |
Student > Doctoral Student | 7 | 6% |
Researcher | 7 | 6% |
Other | 19 | 17% |
Unknown | 22 | 20% |
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Biochemistry, Genetics and Molecular Biology | 29 | 26% |
Neuroscience | 7 | 6% |
Pharmacology, Toxicology and Pharmaceutical Science | 5 | 5% |
Medicine and Dentistry | 5 | 5% |
Other | 7 | 6% |
Unknown | 24 | 22% |