A5073804852- PI3K/AKT/mTOR signaling in cancer
- Protein Kinase Regulation and GTPase Signaling
- Renal and related cancers
- Ubiquitin and proteasome pathways
- Receptor Mechanisms and Signaling
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Polyamine Metabolism and Applications
University of California, San Francisco
2021
University of Basel
2020-2021
Novartis (Switzerland)
2021
Novartis Institutes for BioMedical Research
2021
The structure of mTORC2 reveals the basis its rapamycin insensitivity and explains how stability controls activity.
Abstract The transcription factor PAX8 is critical for the development of thyroid and urogenital system. Comprehensive genomic screens furthermore indicate an additional oncogenic role in renal ovarian cancers. While a plethora PAX8-regulated genes different contexts have been proposed, we still lack mechanistic understanding how engages molecular complexes to drive disease-relevant transcriptional programs. Here show that protein isoforms originating from MECOM locus form complex with PAX8....
The vertebrate-specific DEP domain-containing mTOR interacting protein (DEPTOR), an oncoprotein or tumor suppressor, has important roles in metabolism, immunity, and cancer. It is the only that binds regulates both complexes of mammalian target rapamycin (mTOR), a central regulator cell growth. Biochemical analysis cryo-EM reconstructions DEPTOR bound to human complex 1 (mTORC1) mTORC2 reveal structured regions DEPTOR, PDZ domain tandem (DEPt), are involved interaction. tightly with mildly...
Abstract The protein kinase mammalian target of rapamycin (mTOR) is the central regulator cell growth. Aberrant mTOR signaling linked to cancer, diabetes and neurological disorders. exerts its functions in two distinct multiprotein complexes, mTORC1 mTORC2. Here we report a 3.2 Å resolution cryo-EM reconstruction It reveals entangled folds defining Rictor substrate-binding SIN1 subunits, identifies C-terminal domain as source insensitivity mTORC2, resolves mechanisms for mTORC2 regulation by...