Evidence map›Paper›PMID 30190590›Full record

ArticleNature chemical biology2018

SALL4 mediates teratogenicity as a thalidomide-dependent cereblon substrate.

Mary E Matyskiela, Suzana Couto, Xinde Zheng, Gang Lu, Julia Hui, Katie Stamp, Clifton Drew, Yan Ren, Maria Wang, Aaron Carpenter and 13 more

Abstract read
PubMed Publisher
In one paragraph

Article in Nature chemical biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 158 papers.

0numbers the graph read from it
0cells of the map it votes in
158citing papers in PubMed
11.8field-weighted citation impact, top 1% 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

158 citing papers in PubMed, 333 citations in OpenAlex.

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  18. Induced proximity-based therapeutic modalities.Nature reviews. Drug discovery · 2026
    Review
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  20. Article

98 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

23 authors at 1 institution in 1 country.

Mary E MatyskielaCelgene Corporation, San Diego, CA, USA.
Suzana CoutoCelgene Corporation, San Diego, CA, USA.
Xinde ZhengCelgene Corporation, San Diego, CA, USA.
Gang LuCelgene Corporation, San Diego, CA, USA.
Julia HuiCelgene Corporation, San Diego, CA, USA.
Katie StampCelgene Corporation, San Diego, CA, USA.
Clifton DrewCelgene Corporation, San Diego, CA, USA.
Yan RenCelgene Corporation, San Diego, CA, USA.
Maria WangCelgene Corporation, San Diego, CA, USA.
Aaron CarpenterCelgene Corporation, San Diego, CA, USA.
Chung-Wein LeeCelgene Corporation, San Diego, CA, USA.
Thomas ClaytonCelgene Corporation, San Diego, CA, USA.
Wei FangCelgene Corporation, San Diego, CA, USA.
Chin-Chun LuCelgene Corporation, San Diego, CA, USA.
Mariko RileyCelgene Corporation, San Diego, CA, USA.
Polat AbdubekCelgene Corporation, San Diego, CA, USA.
Kate BleaseCelgene Corporation, San Diego, CA, USA.
James HartkeCelgene Corporation, San Diego, CA, USA.
Gondi KumarCelgene Corporation, San Diego, CA, USA.
Rupert VesseyCelgene Corporation, San Diego, CA, USA.
Mark RolfeCelgene Corporation, San Diego, CA, USA.
Lawrence G HamannCelgene Corporation, San Diego, CA, USA.
Philip P ChamberlainCelgene Corporation, San Diego, CA, USA. pchamberlain@celgene.com.
Bristol-Myers Squibb (Switzerland) · CH

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Targeted protein degradation via small-molecule modulation of cereblon offers vast potential for the development of new therapeutics. Cereblon-binding therapeutics carry the safety risks of thalidomide, which caused an epidemic of severe birth defects characterized by forelimb shortening or phocomelia. Here we show that thalidomide is not teratogenic in transgenic mice expressing human cereblon, indicating that binding to cereblon is not sufficient to cause birth defects. Instead, we identify SALL4 as a thalidomide-dependent cereblon neosubstrate. Human mutations in SALL4 cause Duane-radial ray, IVIC, and acro-renal-ocular syndromes with overlapping clinical presentations to thalidomide embryopathy, including phocomelia. SALL4 is degraded in rabbits but not in resistant organisms such as mice because of SALL4 sequence variations. This work expands the scope of cereblon neosubstrate activity within the formerly 'undruggable' C2H2 zinc finger family and offers a path toward safer therapeutics through an improved understanding of the molecular basis of thalidomide-induced teratogenicity.

Indexed as

Gene Expression RegulationAdaptor Proteins, Signal TransducingAnimalsDNA-Binding ProteinsHomozygoteHumansImmunohistochemistryInduced Pluripotent Stem CellsLigandsMaleMiceMice, TransgenicMutationNerve Tissue ProteinsPeptide HydrolasesProteolysisAdaptor Proteins, Signal TransducingCRBN protein, humanCrbn protein, mouseDNA-Binding ProteinsLigandsNerve Tissue ProteinsPeptide HydrolasesSALL4 protein, humanSall4 protein, mouseTeratogensThalidomideTranscription FactorsUbiquitin-Protein LigasesZFP91 protein, human

Identifiers

PMID30190590
OpenAlexW2891710607

What OpenQuestion holds

Textmetadata
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.