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    1. Biochemistry and Chemical Biology
    2. Computational and Systems Biology

    Mapping the functional versatility and fragility of Ras GTPase signaling circuits through in vitro network reconstitution

    Scott M Coyle, Wendell A Lim
    A systems level reconstitution of H-Ras GTPase signaling reveals a rich space of tunable dynamic outputs and clarifies the consequences of oncogenic perturbations to signaling.
    1. Cancer Biology
    2. Developmental Biology

    Targeting mutant RAS in patient-derived colorectal cancer organoids by combinatorial drug screening

    Carla S Verissimo et al.
    Libraries of patient-derived tumor organoids are a reliable and scalable model system that can help identify and optimize targeted therapies in a pre-clinical setting.
    1. Biochemistry and Chemical Biology
    2. Cell Biology

    ABHD17 proteins are novel protein depalmitoylases that regulate N-Ras palmitate turnover and subcellular localization

    David Tse Shen Lin, Elizabeth Conibear
    Palmitate turnover is controlled by distinct enzyme families with different specificities.
    1. Structural Biology and Molecular Biophysics

    Structural analysis of autoinhibition in the Ras-specific exchange factor RasGRP1

    Jeffrey S Iwig et al.
    A key activator of Ras signaling adopts an autoinhibited, dimeric conformation that is activated by membrane and calcium binding.
    1. Cell Biology
    2. Developmental Biology

    Loss of neurofibromin Ras-GAP activity enhances the formation of cardiac blood islands in murine embryos

    Amanda D Yzaguirre et al.
    Ras-GAP activity suppresses the hemogenic potential of the embryonic heart.
    1. Structural Biology and Molecular Biophysics

    Deconstruction of the Ras switching cycle through saturation mutagenesis

    Pradeep Bandaru et al.
    Sequence conservation in Ras depends strongly on the biochemical network in which it operates, providing a framework for understanding the origin of global selection pressures on proteins.
    1. Biochemistry and Chemical Biology
    2. Structural Biology and Molecular Biophysics

    A Histidine pH sensor regulates activation of the Ras-specific guanine nucleotide exchange factor RasGRP1

    Yvonne Vercoulen et al.
    The Ras activator RasGRP1 that impacts Ras signals in immune cells, leukemias, and colorectal cancer, switches to an active conformation aided by a pH-sensitive histidine residue in a central location of the RasGRP1 molecule.
    1. Developmental Biology
    2. Human Biology and Medicine

    The acinar differentiation determinant PTF1A inhibits initiation of pancreatic ductal adenocarcinoma

    Nathan M Krah et al.
    By regulating acinar cell differentiation, the transcription factor PTF1A acts as a novel class of tumor suppressor in pancreatic cancer.