Dataset Information

A Structure is Worth a Thousand Words: New Insights for RAS and RAF Regulation.

ABSTRACT: The RAS GTPases are frequently mutated in human cancer, with KRAS being the predominant tumor driver. For many years, it has been known that the structure and function of RAS are integrally linked, as structural changes induced by GTP binding or mutational events determine the ability of RAS to interact with regulators and effectors. Recently, a wealth of information has emerged from structures of specific KRAS mutants and from structures of multiprotein complexes containing RAS and/or RAF, an essential effector of RAS. These structures provide key insights regarding RAS and RAF regulation as well as promising new strategies for therapeutic intervention.

Significance

The RAS GTPases are major drivers of tumorigenesis, and for RAS proteins to exert their full oncogenic potential, they must interact with the RAF kinases to initiate ERK cascade signaling. Although binding to RAS is typically a prerequisite for RAF to become an activated kinase, determining the molecular mechanisms by which this interaction results in RAF activation has been a challenging task. A major advance in understanding this process and RAF regulation has come from recent structural studies of various RAS and RAF multiprotein signaling complexes, revealing new avenues for drug discovery.

SUBMITTER: Simanshu DK

PROVIDER: S-EPMC8983508 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

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A Structure is Worth a Thousand Words: New Insights for RAS and RAF Regulation.

Simanshu Dhirendra K DK Morrison Deborah K DK

Cancer discovery 20220401 4

The RAS GTPases are frequently mutated in human cancer, with KRAS being the predominant tumor driver. For many years, it has been known that the structure and function of RAS are integrally linked, as structural changes induced by GTP binding or mutational events determine the ability of RAS to interact with regulators and effectors. Recently, a wealth of information has emerged from structures of specific KRAS mutants and from structures of multiprotein complexes containing RAS and/or RAF, an e ...[more]

PMID: 35046094

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Project description:BackgroundOnline survey-based methods are increasingly used to elicit preferences for healthcare. This digitization creates an opportunity for interactive survey elements, potentially improving respondents' understanding and/or engagement.ObjectiveOur objective was to understand whether, and how, training materials in a survey influenced stated preferences.MethodsAn online discrete-choice experiment (DCE) was designed to elicit public preferences for a new targeted approach to prescribing biologics ("biologic calculator") for rheumatoid arthritis (RA) compared with conventional prescribing. The DCE presented three alternatives, two biologic calculators and a conventional approach (opt out), described by five attributes: delay to treatment, positive predictive value, negative predictive value, infection risk, and cost saving to the national health service. Respondents were randomized to receive training materials as plain text or an animated storyline. Training materials contained information about RA and approaches to treatment and described the biologic calculator. Background questions included sociodemographics and self-reported measures of task difficulty and attribute non-attendance. DCE data were analyzed using conditional and heteroskedastic conditional logit (HCL) models.ResultsIn total, 300 respondents completed the DCE, receiving either plain text (n = 158) or the animated storyline (n = 142). The HCL showed the estimated coefficients for all attributes aligned with a priori expectations and were statistically significant. The scale term was statistically significant, indicating that respondents who received plain-text materials had more random choices. Further tests suggested preference homogeneity after accounting for differences in scale.ConclusionsUsing animated training materials did not change the preferences of respondents, but they appeared to improve choice consistency, potentially allowing researchers to include more complex designs with increased numbers of attributes, levels, alternatives or choice sets.

Dataset Information

A Structure is Worth a Thousand Words: New Insights for RAS and RAF Regulation.

Significance

Publications

A Structure is Worth a Thousand Words: New Insights for RAS and RAF Regulation.

Similar Datasets

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