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  • GFZ Data Services  (1)
  • The American Society for Microbiology (ASM)  (1)
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  • 1
    Publication Date: 2013-03-10
    Description: The immunosuppressant and anticancer drug rapamycin works by inducing inhibitory protein complexes with the kinase mTOR, an important regulator of growth and proliferation. The obligatory accessory partner of rapamycin is believed to be FK506-binding protein 12 (FKBP12). Here we show that rapamycin complexes of larger FKBP family members can tightly bind to mTOR and potently inhibit its kinase activity. Cocrystal structures with FKBP51 and FKBP52 reveal the modified molecular binding mode of these alternative ternary complexes in detail. In cellular model systems, FKBP12 can be functionally replaced by larger FKBPs. When the rapamycin dosage is limiting, mTOR inhibition of S6K phosphorylation can be enhanced by FKBP51 overexpression in mammalian cells, whereas FKBP12 is dispensable. FKBP51 could also enable the rapamycin-induced hyperphosphorylation of Akt, which depended on higher FKBP levels than rapamycin-induced inhibition of S6K phosphorylation. These insights provide a mechanistic rationale for preferential mTOR inhibition in specific cell or tissue types by engaging specific FKBP homologs.
    Print ISSN: 0270-7306
    Electronic ISSN: 1098-5549
    Topics: Biology , Medicine
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  • 2
    Publication Date: 2022-12-06
    Description: The scope of the Science Plan is to describe the scientific background, applications, and activities of the Environmental Mapping and Analysis Program (EnMAP) imaging spectroscopy mission. Primarily, this document addresses scientists and funding institutions, but it may also be of interest to environmental stakeholders and governmental agencies. It is designed to be a living document that will be updated throughout the entire mission lifetime. Chapter 1 provides a brief overview of the principles and current state of imaging spectroscopy. This is followed by an introduction to the EnMAP mission, including its objectives and impact on international programs as well as major environmental and societal challenges. Chapter 2 describes the EnMAP system together with data products and access, calibration/validation, and synergies with other missions. Chapter 3 gives an overview of the major fields of application such as vegetation and forests, geology and soils, coastal and inland waters, cryosphere, urban areas, atmosphere and hazards. Finally, Chapter 4 outlines the scientific exploitation strategy, which includes the strategy for community building and training, preparatory flight campaigns and software developments. A list of abbreviations is provided in the annex to this document and an extended glossary of terms and abbreviations is available on the EnMAP website.
    Language: English
    Type: info:eu-repo/semantics/report
    Format: application/pdf
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