Evidence map›Paper›PMID 42918759›Full record

ArticleCell death & disease2026

OTUD4 stabilizes CYLD and counteracts BCL3 K63-linked polyubiquitination to suppress melanoma progression.

Yuming He, Lin Miao, Yunfang Deng, Yuyao Xue, Zhaohui Liu, Zhiming Sun, Chujing He, Hao Feng, Jiabing Li, Yuqiao Cai and 3 more

Abstract read
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In one paragraph

Article in Cell death & disease, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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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

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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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

13 authors.

Yuming He *The National & Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha, China.ORCID http://orcid.org/0009-0008-2003-5186
Lin Miao *The National & Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha, China.
Yunfang DengThe National & Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha, China.
Yuyao XueThe National & Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha, China.
Zhaohui LiuThe National & Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha, China.ORCID http://orcid.org/0009-0000-3618-310X
Zhiming SunThe National & Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha, China.ORCID http://orcid.org/0009-0002-0937-2815
Chujing HeThe National & Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha, China.
Hao FengDepartment of Dermatology, Hunan Provincial People's Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha, China.
Jiabing LiThe National & Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha, China.
Yuqiao CaiThe National & Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha, China.
Yaoyu GuThe National & Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha, China.
Ke LiDepartment of Dermatology, Hunan Provincial People's Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha, China.
Yu ZhaoThe National & Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha, China. smile_zhao@hotmail.com.ORCID http://orcid.org/0009-0000-9856-3917

Funding

Natural Science Foundation of Hunan Province (Hunan Provincial Natural Science Foundation) 2026JJ50154
6 · The paper itself

Abstract

Melanoma is a highly aggressive malignancy in which dysregulated ubiquitin-dependent signaling contributes to tumor progression. OTUD4 is frequently downregulated in melanoma, but the functional significance of this alteration remains unclear. Here, we identify OTUD4 as a dual-mode deubiquitinase that suppresses melanoma progression by coordinating K48- and K63-linked polyubiquitination. OTUD4 directly binds and stabilizes CYLD by counteracting K48-linked polyubiquitination, whereas it independently binds BCL3 and counteracts BCL3 K63-linked polyubiquitination. OTUD4 depletion promotes BCL3 ubiquitination and nuclear translocation in melanoma cells, leading to increased melanoma cell proliferation and tumor growth in clonogenic and xenograft assays. Clinically, expression of OTUD4 and CYLD progressively decreases from normal skin through benign nevi to melanoma, with a further reduction in highly metastatic tumors. Reduced expression of OTUD4 and CYLD is associated with poor prognosis in patients with melanoma. Together, these results reveal an OTUD4-CYLD-BCL3 regulatory axis in melanoma, in which OTUD4 stabilizes CYLD and inhibits BCL3 activity.

Indexed as

Deubiquitinating Enzyme CYLDMelanomaProto-Oncogene ProteinsAnimalsB-Cell Lymphoma 3 ProteinCell Line, TumorCell ProliferationDisease ProgressionHumansMiceMice, NudeProtein StabilityUbiquitinationB-Cell Lymphoma 3 ProteinBCL3 protein, humanCYLD protein, humanDeubiquitinating Enzyme CYLDProto-Oncogene Proteins

Identifiers

PMID42918759

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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.