Evidence map›Paper›PMID 31006619›Full record

ArticleCell chemical biology2019

A Chemical Strategy for Protease Substrate Profiling.

Andrew R Griswold, Paolo Cifani, Sahana D Rao, Abram J Axelrod, Matthew M Miele, Ronald C Hendrickson, Alex Kentsis, Daniel A Bachovchin

Open access · bronzeAbstract read
In one paragraph

Article in Cell chemical biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.

0numbers the graph read from it
0cells of the map it votes in
39citing papers in PubMed
3.9field-weighted citation impact, top 5% of its field
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

39 citing papers in PubMed, 77 citations in OpenAlex.

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  11. Integrating the analysis of human biopsies using post-translational modifications proteomics.Protein science : a publication of the Protein Society · 2024
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 2 institutions in 1 country.

Andrew R GriswoldWeill Cornell/Rockefeller/Sloan Kettering Tri-Institutional MD-PhD Program, New York, NY 10065, USA; Pharmacology Program, Weill Cornell Graduate School of Medical Sciences, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Paolo CifaniMolecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Sahana D RaoTri-Institutional PhD Program in Chemical Biology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Abram J AxelrodChemical Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Matthew M MieleProteomics Core Laboratory, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Ronald C HendricksonProteomics Core Laboratory, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Alex KentsisPharmacology Program, Weill Cornell Graduate School of Medical Sciences, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Tri-Institutional PhD Program in Chemical Biology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Department of Pediatrics, Memorial Sloan Kettering Cancer Center and Weill Medical College of Cornell University, New York, NY 10065, USA.
Daniel A BachovchinPharmacology Program, Weill Cornell Graduate School of Medical Sciences, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Tri-Institutional PhD Program in Chemical Biology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Chemical Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. Electronic address: bachovcd@mskcc.org.
Memorial Sloan Kettering Cancer Center · USTri-Institutional PhD Program in Chemical Biology · US

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Hongbiao Carl Lekaye · 1985 to 2026
$347.4M
Weill Cornell/Rockefeller/Sloan-Kettering MST ProgramT32GM007739 · NIGMS · WEILL MEDICAL COLL OF CORNELL UNIV · PI HSU, KATHARINE C · 1985 to 2023
$51.1M
ABERRANT SIGNALING IN ACUTE MYELOID LEUKEMIAR01CA204396 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI KENTSIS, ALEX · 2016 to 2025
$5.2M
Characterizing the Mechanism of DPP8/9 Inhibitor-Induced PyroptosisR01AI137168 · NIAID · SLOAN-KETTERING INST CAN RESEARCH · PI Daniel Bachovchin · 2018 to 2026
$4.3M
Phosphoproteomic signatures for early detection and stratification of AMLR21CA188881 · NCI · DANA-FARBER CANCER INST · PI KENTSIS, ALEX, MARTO, JARROD A. · 2015 to 2016
$420k
NCI NIH HHS P30 CA008748NCI NIH HHS R01 CA204396NCI NIH HHS R21 CA188881NIAID NIH HHS R01 AI137168NIGMS NIH HHS T32 GM007739Wellcome Trust
6 · The paper itself

Abstract

The dipeptidyl peptidases (DPPs) regulate hormones, cytokines, and neuropeptides by cleaving dipeptides after proline from their amino termini. Due to technical challenges, many DPP substrates remain unknown. Here, we introduce a simple method, termed CHOPS (chemical enrichment of protease substrates), for the discovery of protease substrates. CHOPS exploits a 2-pyridinecarboxaldehyde (2PCA)-biotin probe, which selectively biotinylates protein N-termini except those with proline in the second position. CHOPS can, in theory, discover substrates for any protease, but is particularly well suited to discover canonical DPP substrates, as cleaved but not intact DPP substrates can be identified by gel electrophoresis or mass spectrometry. Using CHOPS, we show that DPP8 and DPP9, enzymes that control the Nlrp1 inflammasome through an unknown mechanism, do not directly cleave Nlrp1. We further show that DPP9 robustly cleaves short peptides but not full-length proteins. More generally, this work delineates a practical technology for identifying protease substrates, which we anticipate will complement available "N-terminomic" approaches.

Indexed as

Adaptor Proteins, Signal TransducingApoptosis Regulatory ProteinsBiotinDipeptidasesDipeptidyl-Peptidases and Tripeptidyl-PeptidasesHumansInflammasomesMolecular StructureNLR ProteinsPeptide HydrolasesPyridinesSubstrate SpecificityAdaptor Proteins, Signal TransducingApoptosis Regulatory ProteinsBiotinDipeptidasesDipeptidyl-Peptidases and Tripeptidyl-PeptidasesDPP8 protein, humanDPP9 protein, humanInflammasomesNLRP1 protein, humanNLR ProteinsPeptide HydrolasespyridinecarboxaldehydePyridineschemical probesmass spectrometry-based proteomicsNlrp1 inflammasomeN-terminal modificationprotease substrates

Identifiers

PMID31006619
PMCPMC6588500
OpenAlexW2936148319

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.