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Your search keyword '"Schaffer, Bethany E."' showing total 25 results
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25 results on '"Schaffer, Bethany E."'

2. Identification of AMPK Phosphorylation Sites Reveals a Network of Proteins Involved in Cell Invasion and Facilitates Large-Scale Substrate Prediction

Author

Schaffer, Bethany E, Levin, Rebecca S, Hertz, Nicholas T, Maures, Travis J, Schoof, Michael L, Hollstein, Pablo E, Benayoun, Bérénice A, Banko, Max R, Shaw, Reuben J, Shokat, Kevan M, and Brunet, Anne

Subjects
Biochemistry and Cell Biology, Biological Sciences, 1.1 Normal biological development and functioning, 2.1 Biological and endogenous factors, Generic health relevance, AMP-Activated Protein Kinases, Animals, Cell Adhesion, Cell Movement, Extracellular Matrix, Humans, Oncogene Proteins, Peptides, Phosphorylation, Protein Interaction Maps, Single-Cell Analysis, Substrate Specificity, Medical Biochemistry and Metabolomics, Endocrinology & Metabolism, Biochemistry and cell biology, Medical biochemistry and metabolomics
Abstract

AMP-activated protein kinase (AMPK) is a central energy gauge that regulates metabolism and has been increasingly involved in non-metabolic processes and diseases. However, AMPK's direct substrates in non-metabolic contexts are largely unknown. To better understand the AMPK network, we use a chemical genetics screen coupled to a peptide capture approach in whole cells, resulting in identification of direct AMPK phosphorylation sites. Interestingly, the high-confidence AMPK substrates contain many proteins involved in cell motility, adhesion, and invasion. AMPK phosphorylation of the RHOA guanine nucleotide exchange factor NET1A inhibits extracellular matrix degradation, an early step in cell invasion. The identification of direct AMPK phosphorylation sites also facilitates large-scale prediction of AMPK substrates. We provide an AMPK motif matrix and a pipeline to predict additional AMPK substrates from quantitative phosphoproteomics datasets. As AMPK is emerging as a critical node in aging and pathological processes, our study identifies potential targets for therapeutic strategies.

Published
2015

17. Glutamine deprivation triggers NAGK-dependent hexosamine salvage

Author

Campbell, Sydney, primary, Mesaros, Clementina, additional, Izzo, Luke, additional, Affronti, Hayley, additional, Noji, Michael, additional, Schaffer, Bethany E, additional, Tsang, Tiffany, additional, Sun, Kathryn, additional, Trefely, Sophie, additional, Kruijning, Salisa, additional, Blenis, John, additional, Blair, Ian A, additional, and Wellen, Kathryn E, additional

Published
2021
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18. Author response: Glutamine deprivation triggers NAGK-dependent hexosamine salvage

Author

Campbell, Sydney, primary, Mesaros, Clementina, additional, Izzo, Luke, additional, Affronti, Hayley, additional, Noji, Michael, additional, Schaffer, Bethany E, additional, Tsang, Tiffany, additional, Sun, Kathryn, additional, Trefely, Sophie, additional, Kruijning, Salisa, additional, Blenis, John, additional, Blair, Ian A, additional, and Wellen, Kathryn E, additional

Published
2021
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19. Glutamine deprivation triggers NAGK-dependent hexosamine salvage

Author

Campbell, Sydney L., primary, Mesaros, Clementina, additional, Izzo, Luke, additional, Affronti, Hayley, additional, Noji, Michael, additional, Schaffer, Bethany E., additional, Tsang, Tiffany, additional, Sun, Kathryn, additional, Trefely, Sophie, additional, Kruijning, Salisa, additional, Blenis, John, additional, Blair, Ian A., additional, and Wellen, Kathryn E., additional

Published
2020
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20. Notch signaling inhibits hepatocellular carcinoma following inactivation of the RB pathway

Author

Viatour, Patrick, primary, Ehmer, Ursula, additional, Saddic, Louis A., additional, Dorrell, Craig, additional, Andersen, Jesper B., additional, Lin, Chenwei, additional, Zmoos, Anne-Flore, additional, Mazur, Pawel K., additional, Schaffer, Bethany E., additional, Ostermeier, Austin, additional, Vogel, Hannes, additional, Sylvester, Karl G., additional, Thorgeirsson, Snorri S., additional, Grompe, Markus, additional, and Sage, Julien, additional

Published
2011
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21. Characterization of the cell of origin for small cell lung cancer

Author

Park, Kwon-Sik, primary, Liang, Mei-Chih, additional, Raiser, David M., additional, Zamponi, Raffaella, additional, Roach, Rebecca R., additional, Curtis, Stephen J., additional, Walton, Zandra, additional, Schaffer, Bethany E., additional, Roake, Caitlin M., additional, Zmoos, Anne-Flore, additional, Kriegel, Christina, additional, Wong, Kwok-Kin, additional, Sage, Julien, additional, and Kim, Carla F., additional

Published
2011
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25. Notch signaling inhibits hepatocellular carcinoma following inactivation of the RB pathway.

Author

Viatour P, Ehmer U, Saddic LA, Dorrell C, Andersen JB, Lin C, Zmoos AF, Mazur PK, Schaffer BE, Ostermeier A, Vogel H, Sylvester KG, Thorgeirsson SS, Grompe M, and Sage J

Subjects
Animals, Carcinoma, Hepatocellular pathology, Cell Line, Cell Proliferation, E2F Transcription Factors genetics, E2F Transcription Factors metabolism, Gene Expression Profiling, Humans, Liver Neoplasms pathology, Mice, Mice, Inbred C57BL, Mice, Knockout, Microarray Analysis, Receptors, Notch genetics, Retinoblastoma Protein genetics, Stem Cells physiology, Transcription, Genetic, Carcinoma, Hepatocellular physiopathology, Liver Neoplasms physiopathology, Receptors, Notch metabolism, Retinoblastoma Protein metabolism, Signal Transduction physiology
Abstract

Hepatocellular carcinoma (HCC) is the third cancer killer worldwide with >600,000 deaths every year. Although the major risk factors are known, therapeutic options in patients remain limited in part because of our incomplete understanding of the cellular and molecular mechanisms influencing HCC development. Evidence indicates that the retinoblastoma (RB) pathway is functionally inactivated in most cases of HCC by genetic, epigenetic, and/or viral mechanisms. To investigate the functional relevance of this observation, we inactivated the RB pathway in the liver of adult mice by deleting the three members of the Rb (Rb1) gene family: Rb, p107, and p130. Rb family triple knockout mice develop liver tumors with histopathological features and gene expression profiles similar to human HCC. In this mouse model, cancer initiation is associated with the specific expansion of populations of liver stem/progenitor cells, indicating that the RB pathway may prevent HCC development by maintaining the quiescence of adult liver progenitor cells. In addition, we show that during tumor progression, activation of the Notch pathway via E2F transcription factors serves as a negative feedback mechanism to slow HCC growth. The level of Notch activity is also able to predict survival of HCC patients, suggesting novel means to diagnose and treat HCC.

Published
2011
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