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 % |
---|---|---|
United States | 5 | 50% |
Saudi Arabia | 1 | 10% |
Unknown | 4 | 40% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 7 | 70% |
Science communicators (journalists, bloggers, editors) | 2 | 20% |
Scientists | 1 | 10% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 3 | 3% |
Spain | 1 | <1% |
United Kingdom | 1 | <1% |
Unknown | 104 | 95% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 27 | 25% |
Student > Master | 14 | 13% |
Student > Bachelor | 13 | 12% |
Student > Doctoral Student | 7 | 6% |
Researcher | 7 | 6% |
Other | 20 | 18% |
Unknown | 21 | 19% |
Readers by discipline | Count | As % |
---|---|---|
Agricultural and Biological Sciences | 33 | 30% |
Biochemistry, Genetics and Molecular Biology | 29 | 27% |
Neuroscience | 7 | 6% |
Medicine and Dentistry | 5 | 5% |
Pharmacology, Toxicology and Pharmaceutical Science | 4 | 4% |
Other | 8 | 7% |
Unknown | 23 | 21% |