Evidence map›Paper›PMID 40953270›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2025

An in vitro BRAF activation assay elucidates molecular mechanisms driving disassembly of the autoinhibited BRAF state.

Daniel A Ritt, David E Durrant, Matthew R Drew, Suzanne I Sandin, Juliana A Martinez Fiesco, Xiaohua Zhang, Fikret Aydin, Timothy S Carpenter, Grace M Scheidemantle, Robert A D'Ippolito and 16 more

Abstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

8 citing papers in PubMed.

  1. Review
  2. Free Energy and Flexibility Analysis of Autoinhibited Human BRAF.Journal of chemical information and modeling · 2026
    Article
  3. Article
  4. Restoring the 14-3-3/CRAF regulatory interaction in Noonan syndrome using molecular glues.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  5. Article
  6. Article
  7. QnAs with Deborah K. Morrison.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  8. An in vitro BRAF activation assay elucidates molecular mechanisms driving disassembly of the autoinhibited BRAF state.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

26 authors.

Daniel A RittLaboratory of Cell and Developmental Signaling, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702.
David E DurrantLaboratory of Cell and Developmental Signaling, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702.
Matthew R DrewNational Cancer Institute RAS Initiative, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, MD 21702.ORCID 0000-0002-3954-6671
Suzanne I SandinNational Cancer Institute RAS Initiative, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, MD 21702.
Juliana A Martinez FiescoCenter for Structural Biology, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702.
Xiaohua ZhangBiosciences and Biotechnology Division, Physical and Life Sciences Directorate, Lawrence Livermore National Laboratory, Livermore, CA 94550.
Fikret AydinBiosciences and Biotechnology Division, Physical and Life Sciences Directorate, Lawrence Livermore National Laboratory, Livermore, CA 94550.
Timothy S CarpenterBiosciences and Biotechnology Division, Physical and Life Sciences Directorate, Lawrence Livermore National Laboratory, Livermore, CA 94550.ORCID 0000-0001-7848-9983
Grace M ScheidemantleNational Cancer Institute RAS Initiative, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, MD 21702.
Robert A D'IppolitoNational Cancer Institute RAS Initiative, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, MD 21702.
Alexandria L SohnNational Cancer Institute RAS Initiative, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, MD 21702.
Caroline J DeHartNational Cancer Institute RAS Initiative, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, MD 21702.
Rebika ShresthaNational Cancer Institute RAS Initiative, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, MD 21702.
Kelly SneadNational Cancer Institute RAS Initiative, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, MD 21702.
Jenna HullNational Cancer Institute RAS Initiative, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, MD 21702.
Jeremy O B TempkinBiosciences and Biotechnology Division, Physical and Life Sciences Directorate, Lawrence Livermore National Laboratory, Livermore, CA 94550.
Yue YangBiosciences and Biotechnology Division, Physical and Life Sciences Directorate, Lawrence Livermore National Laboratory, Livermore, CA 94550.
Felice C LightstoneBiosciences and Biotechnology Division, Physical and Life Sciences Directorate, Lawrence Livermore National Laboratory, Livermore, CA 94550.
Frederick H StreitzBiosciences and Biotechnology Division, Physical and Life Sciences Directorate, Lawrence Livermore National Laboratory, Livermore, CA 94550.
Ping ZhangCenter for Structural Biology, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702.ORCID 0000-0002-0340-281X
Thomas J TurbyvilleNational Cancer Institute RAS Initiative, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, MD 21702.
Andrew G StephenNational Cancer Institute RAS Initiative, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, MD 21702.ORCID 0000-0002-8259-621X
Dominic EspositoNational Cancer Institute RAS Initiative, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, MD 21702.ORCID 0000-0002-9987-1687
Helgi I IngólfssonBiosciences and Biotechnology Division, Physical and Life Sciences Directorate, Lawrence Livermore National Laboratory, Livermore, CA 94550.
Dwight V NissleyNational Cancer Institute RAS Initiative, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, MD 21702.ORCID 0000-0001-7523-116X
Deborah K MorrisonLaboratory of Cell and Developmental Signaling, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702.ORCID 0000-0002-1928-1987

Funding

WORK ORDER 126643 B539 EXPAND IC SUITE75N91019D00024 · NIAID · LEIDOS BIOMEDICAL RESEARCH, INC. · PI BRISCOE, LYNN · 2019 to 2025
$3932.6M
Regulation of Ras-Dependent Signal Transduction PathwaysZIABC010329 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI MORRISON, DEBORAH · 2009 to 2025
$16.1M
Structures and Mechanisms of Kinase Signaling ComplexesZIABC011744 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI ZHANG, PING · 2017 to 2025
$12.6M
DOE | NNSA | Lawrence Livermore National Laboratory (LLNL) DE-AC52-07NA27344DOE | SC | Oak Ridge National Laboratory (ORNL) DE-AC05-00OR22725HHS | NIH | National Cancer Institute (NCI) ZIA BC 010329HHS | NIH | National Cancer Institute (NCI) ZIA VC 011744Intramural NIH HHS ZIA BC010329Intramural NIH HHS ZIA BC011744NCI NIH HHS 75N91019D00024
6 · The paper itself

Abstract

The RAF kinases (ARAF, BRAF, and CRAF) are essential components of the RAS-ERK signaling pathway, which controls vital cellular processes and is frequently dysregulated in human disease. Notably, mutations that alter BRAF function are prominent drivers of human cancer and certain RASopathy disorders, making BRAF an important target for therapeutic intervention. Despite extensive research, several aspects of BRAF regulation remain unclear. In this study, we developed an in vitro BRAF activation assay using purified autoinhibited BRAF:14-3-3

Indexed as

Proto-Oncogene Proteins B-rafEnzyme ActivationHumansLiposomesMAP Kinase Signaling SystemMutationPhosphatidylserinesPhosphorylationProto-Oncogene Proteins p21(ras)BRAF protein, humanKRAS protein, humanLiposomesPhosphatidylserinesProto-Oncogene Proteins B-rafProto-Oncogene Proteins p21(ras)BRAFKRASRAF kinasesRAS GTPasesignal transduction

Identifiers

PMID40953270
PMCPMC12478067

What OpenQuestion holds

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LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.