Evidence map›Paper›PMID 42348677›Full record

ArticleScience (New York, N.Y.)2026

Ubiquitin-like proteins NEDD8 and SUMO2 control epithelial homeostasis, regeneration, and inflammation.

Mårten C G Winge, Leandra V Jackrazi, Douglas F Porter, Suhas Srinivasan, Vanessa Lopez-Pajares, Dayan J Li, Benjamin Pham, Aubrey Houser, Spencer H Cha, Robin M Meyers and 9 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Science (New York, N.Y.), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Article
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

19 authors.

Mårten C G Winge *Program in Epithelial Biology, Stanford University, Stanford, CA, USA.ORCID 0000-0001-6119-6009
Leandra V Jackrazi *Program in Epithelial Biology, Stanford University, Stanford, CA, USA.ORCID 0000-0003-2077-329X
Douglas F PorterProgram in Epithelial Biology, Stanford University, Stanford, CA, USA.ORCID 0000-0001-9491-8258
Suhas SrinivasanProgram in Epithelial Biology, Stanford University, Stanford, CA, USA.ORCID 0000-0001-8309-9648
Vanessa Lopez-PajaresProgram in Epithelial Biology, Stanford University, Stanford, CA, USA.ORCID 0000-0001-8538-344X
Dayan J LiProgram in Epithelial Biology, Stanford University, Stanford, CA, USA.ORCID 0000-0001-8154-9019
Benjamin PhamDepartment of Surgery, Stanford University, Stanford, CA, USA.ORCID 0000-0003-2441-9618
Aubrey HouserDepartment of Dermatology, Icahn School of Medicine at Mount Sinai, New York, USA.ORCID 0000-0002-3373-6124
Spencer H ChaProgram in Epithelial Biology, Stanford University, Stanford, CA, USA.ORCID 0009-0000-9175-8914
Robin M MeyersProgram in Epithelial Biology, Stanford University, Stanford, CA, USA.ORCID 0000-0002-1802-7231
Lisa A KoProgram in Epithelial Biology, Stanford University, Stanford, CA, USA.ORCID 0000-0002-3732-0580
Luca DucoliProgram in Epithelial Biology, Stanford University, Stanford, CA, USA.
Weili MiaoProgram in Epithelial Biology, Stanford University, Stanford, CA, USA.ORCID 0000-0002-7487-8962
Lindsey M MeserveyProgram in Epithelial Biology, Stanford University, Stanford, CA, USA.ORCID 0000-0001-9436-7185
Brian J ZarnegarProgram in Epithelial Biology, Stanford University, Stanford, CA, USA.
Mark SmithSarafan ChEM-H, Stanford University, Stanford, CA, USA.ORCID 0000-0002-0313-5723
Andrew L JiDepartment of Dermatology, Icahn School of Medicine at Mount Sinai, New York, USA.ORCID 0000-0001-9688-5680
Michael T LongakerDepartment of Surgery, Stanford University, Stanford, CA, USA.ORCID 0000-0003-1430-8914
Paul A KhavariProgram in Epithelial Biology, Stanford University, Stanford, CA, USA.ORCID 0000-0003-0098-4989

Funding

REGULATORS OF EPIDERMAL GENE EXPRESSIONR01AR045192 · NIAMS · STANFORD UNIVERSITY · PI PAUL KHAVARI · 1999 to 2026
$9.9M
Signaling Regulators of Epithelial Homeostasis and NeoplasiaR01AR049737 · NIAMS · STANFORD UNIVERSITY · PI PAUL KHAVARI · 2004 to 2026
$7.1M
BLRD VA I01 BX001409NIAMS NIH HHS R01 AR045192NIAMS NIH HHS R01 AR049737
6 · The paper itself

Abstract

Stratified epithelial differentiation involves transcriptional and proteomic remodeling. Here, multiomic profiling implicated ubiquitin and related posttranslational networks in differentiation dynamics. Systematic perturbation of ubiquitin-like machinery in primary human keratinocytes which uncovered opposite functions of neural-precursor-cell-expressed, developmentally down-regulated 8 (NEDD8) and small ubiquitin-related modifier 2 (SUMO2). Generation of conditional knockout mice established essential roles for NEDD8 in progenitor maintenance, skin regeneration, and inflammation, whereas SUMO2 was required for differentiation. Beyond ubiquitin-proteasome-concordant changes, NEDD8 directed proteomic regulation correlated with RNA abundance. Integration of immunoprecipitation- mass spectrometry with genome-wide suppressor screening revealed context-specific NEDDylation dependencies. Among effectors, heterogeneous nuclear ribonucleoprotein U (HNRNPU) emerged as a posttranscriptional regulator of epithelial cell state whose RNA binding repertoire was modulated by NEDDylation. Thus, NEDD8 and SUMO2 play opposite roles in epithelial homeostasis, regeneration, and inflammation, demonstrating multiple ways ubiquitin-like networks govern tissue homeostasis.

Indexed as

InflammationKeratinocytesRegenerationSmall Ubiquitin-Related Modifier ProteinsUbiquitinsAnimalsCell DifferentiationCells, CulturedHomeostasisHumansMiceMice, KnockoutNEDD8 ProteinNEDD8 ProteinNEDD8 protein, humanNedd8 protein, mouseSmall Ubiquitin-Related Modifier ProteinsSUMO2 protein, humanUbiquitins

Identifiers

PMID42348677
PMCPMC13421985

What Socratic 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 Socratic graph.