Evidence map›Paper›PMID 40667143›Full record

ArticlebioRxiv : the preprint server for biology2025

The contribution of native protein complexes to targeted protein degradation.

Lorraine Glennie, Nicole Curnutt, Tyrell Cartwright, Karen Dunbar, Brune Le Chatelier, Nicola T Wood, Thomas J Macartney, Christina M Woo, Gopal P Sapkota

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Review
  2. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors.

Lorraine GlennieMedical Research Council Phosphorylation & Ubiquitylation Unit (MRC-PPU), School of Life Sciences, University of Dundee, Dow Street, Dundee, DD1 5EH, Scotland, UK.
Nicole CurnuttDepartment of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA and Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Tyrell CartwrightMedical Research Council Phosphorylation & Ubiquitylation Unit (MRC-PPU), School of Life Sciences, University of Dundee, Dow Street, Dundee, DD1 5EH, Scotland, UK.
Karen DunbarMedical Research Council Phosphorylation & Ubiquitylation Unit (MRC-PPU), School of Life Sciences, University of Dundee, Dow Street, Dundee, DD1 5EH, Scotland, UK.
Brune Le ChatelierMedical Research Council Phosphorylation & Ubiquitylation Unit (MRC-PPU), School of Life Sciences, University of Dundee, Dow Street, Dundee, DD1 5EH, Scotland, UK.
Nicola T WoodMedical Research Council Phosphorylation & Ubiquitylation Unit (MRC-PPU), School of Life Sciences, University of Dundee, Dow Street, Dundee, DD1 5EH, Scotland, UK.
Thomas J MacartneyMedical Research Council Phosphorylation & Ubiquitylation Unit (MRC-PPU), School of Life Sciences, University of Dundee, Dow Street, Dundee, DD1 5EH, Scotland, UK.ORCID 0000-0002-6745-183X
Christina M WooDepartment of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA and Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.ORCID 0000-0001-8687-9105
Gopal P SapkotaMedical Research Council Phosphorylation & Ubiquitylation Unit (MRC-PPU), School of Life Sciences, University of Dundee, Dow Street, Dundee, DD1 5EH, Scotland, UK.ORCID 0000-0001-9931-3338

Funding

Project 2: Combined personal neoantigen-targeting cancer vaccines with immune checkpoint blockade for ovarian cancerP50CA240243 · NCI · DANA-FARBER CANCER INST · PI CASTRO, CESAR M · 2020 to 2024
$11.5M
NCI NIH HHS P50 CA240243
6 · The paper itself

Abstract

Targeted protein degradation (TPD) destroys proteins of interest (POIs) by hijacking the cellular proteolytic machinery. Most proteins in cells exist and function as part of multi-protein or macromolecular complexes, thereby allowing a single protein to control multiple biological processes. Therefore, when a small molecule degrader induces proximity between an E3 ligase and the POI, the macromolecular context of the POI potentially influences the degradation outcomes of the POI and of the complex components. Here, we explore degradation of the eight CK1α-SACK1(A-H) (formerly known as FAM83A-H) complexes initiated by molecular glue degraders primarily designed to target Ser/Thr kinase CK1α. We demonstrate that lenalidomide-derived degraders DEG-77 and SJ3149, which selectively target the CK1α isoform, co-degrade multiple SACK1(A-H) proteins. We show that the degradation of SACK1(A-H) proteins by DEG-77 and SJ3149 requires CK1α, the CUL4A

Identifiers

PMID40667143
PMCPMC12262682

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.