Results 61 to 70 of about 63,525 (265)

Multistep regulation of TFEB by MTORC1 [PDF]

Autophagy, 2017
The master regulator of lysosome biogenesis, TFEB, is regulated by MTORC1 through phosphorylation at S211, and a S211A mutation increases nuclear localization. However, TFEBS211A localizes diffusely in both cytoplasm and nucleus and, as we show, retains regulation by MTORC1.
Vega-Rubín-de-Celis, Silvia, Peña-Llopis, Samuel, Konda, Meghan, Brugarolas, James   +3 more
openaire   +3 more sources

mTORC2 Phosphorylation of GSDME‐N Drives Cullin4B‐Mediated Proteasomal Degradation to Suppress Pyroptosis and Confer Radioresistance in Small Cell Lung Cancer

Advanced Science, EarlyView.
Radioresistance severely limits the efficacy of therapies for small cell lung cancer (SCLC). This study reveals a novel mechanism of resistance driven by the active suppression of pyroptosis. Specifically, the mTORC2 complex directly phosphorylates GSDME‐N and promotes its CUL4B‐mediated ubiquitination and proteasomal degradation.
Qing‐qing Xu, Ci‐ming Sun, Sui‐xian Zhang, Rui Li, Chen‐fei Wu, Zai‐shan Lin, Li Li, Run‐zhe Chen, Qi‐wen Li, Yuan‐yuan Chen, Xuan Li, Ming Chen   +11 more
wiley   +1 more source

A Brain‐Penetrant Nanobody Reveals GSK3β‐Driven Proline‐Directed Phosphorylation as a Master Regulator of Ischemic Neurodegeneration

Advanced Science, EarlyView.
A brain‐targeted nanoparticle enables delivery of a therapeutic nanobody (Nb.29E9) that inhibits pathogenic GSK3β signaling. This intervention restores AMPK/mTORC1/TGFβ homeostasis, attenuates neuroinflammation and oxidative stress, and promotes long‐term functional recovery after ischemic stroke.
Lan Li, Muyang Li, Lei Sun, Ying Yang, Yuanshun Wu, Ziyi Yin, Anni Wang, Peiyang Zhou, Shaoxiang Luo, Jian Chen, Jun Qin, Zhibing Ai, Zilong Yuan, Zhiqiang Dong, Min Zhang   +14 more
wiley   +1 more source

Escaping mTOR inhibition for cancer therapy: Tumor suppressor functions of mTOR

Molecular & Cellular Oncology, 2017
A master promoter of cell growth, mammalian target of rapamycin (mTOR) is upregulated in a large percentage of cancer cells. Still, targeting mTOR using rapamycin has a limited outcome in patients. Our recent results highlight the additional role of mTOR
Victor H. Villar, Tra Ly Nguyen, Silvia Terés, Clément Bodineau, Raúl V. Durán   +4 more
doaj   +1 more source

Radiation‐Induced Tumor‐Intrinsic LTβR N‐Glycosylation Suppresses Pyroptosis Through TRIM28‐Mediated PCBP2 SUMOylation to Promote Gastric Cancer Radioresistance

Advanced Science, EarlyView.
Radiotherapy triggers LTβR N‐glycosylation, enhancing its overall protein stability and nuclear retention. This accumulation drives TRIM28‐mediated PCBP2 SUMOylation, suppressing pyroptosis and conferring gastric cancer radioresistance. Therapeutically, a targeted nanoplatform (cRGD‐Lipo@EMD) effectively disrupts this regulatory axis, offering a highly
Weijie Zang, Yunlong Ji, Chunwang Zhou, Xiwen Li, Zhuang Lu, Guangze Zhang, Yu Chen, Wanjiang Xue, Yilin Hu   +8 more
wiley   +1 more source

Exosome Release Is Regulated by mTORC1 [PDF]

Advanced Science, 2018
AbstractExosomes are small membrane‐bound vesicles released into extracellular spaces by many types of cells. These nanovesicles carry proteins, mRNA, and miRNA, and are involved in cell waste management and intercellular communication. In the present study, it is shown that exosome release, which leads to net loss of cellular membrane and protein ...
Zou, Wenchong, Lai, Mingqiang, Zhang, Yue, Zheng, Lei, Xing, Zhe, Li, Ting, Zou, Zhipeng, Song, Qiancheng, Zhao, Xiaoyang, Xia, Laixin, Yang, Jian, Liu, Anling, Zhang, Han, Cui, Zhong‐Kai, Jiang, Yu, Bai, Xiaochun   +15 more
openaire   +2 more sources

Adipocyte Myoglobin Is a Determinant of Energy Expenditure and a Potential Target to Limit Obesity

Advanced Science, EarlyView.
Myoglobin, known as a muscle oxygen‐carrying protein, is shown to play a key role in fat cells that burn energy. Loss of myoglobin reduces the body's ability to generate heat and increases obesity risk, while restoring it improves metabolism. The study identifies myoglobin as a regulator of fat burning and a potential target to enhance energy ...
Christian Strehlau, Helen Broghammer, Claudia Gebhardt, Anne Hoffmann, Tobias Hagemann, Şeyma Midilli, Rachel S. Zimmer, Kristin Schubert, Vasiliki Karagiannakou, Anastasia Georgiadi, Mario Ost, Martin Krüger, Lisa Roth, Kerstin Krause, Nora Klöting, Maria Keller, Martin Wabitsch, Rima Nuwayhid, Roland H. Stimson, Michael Stumvoll, Matthias Blüher, Juliane Weiner, John T. Heiker   +22 more
wiley   +1 more source

An mTORC1 to HRI signaling axis promotes cytotoxicity of proteasome inhibitors in multiple myeloma

Cell Death and Disease, 2022
Multiple myeloma (MM) causes approximately 20% of deaths from blood cancers. Notwithstanding significant therapeutic progress, such as with proteasome inhibitors (PIs), MM remains incurable due to the development of resistance.
Odai Darawshi, Barbara Muz, Shiri Gershon Naamat, Bellam Praveen, Mohamed Mahameed, Karin Goldberg, Priya Dipta, Miriam Shmuel, Francesca Forno, Shatha Boukeileh, Hadas Pahima, Julia Hermann, Marc S. Raab, Alexandra M. Poos, Niels Weinhold, Chaggai Rosenbluh, Moshe E. Gatt, Wilhelm Palm, Abdel Kareem Azab, Boaz Tirosh   +19 more
doaj   +1 more source

Genetic and Environmental Contributions to Autism Spectrum Disorder Through Mechanistic Target of Rapamycin

Biological Psychiatry Global Open Science, 2022
Autism spectrum disorder (ASD) is a neurodevelopmental disorder that affects an individual’s reciprocal social interaction and communication ability.
Atsushi Sato, Kazutaka Ikeda
doaj   +1 more source

mTORC1 Regulates Glutamine Metabolism [PDF]

Cancer Discovery, 2013
Abstract mTORC1 stimulates glutamine metabolism by inducing glutamate dehydrogenase (GDH).
openaire   +2 more sources