ArticleMolecular biology of the cell2018
WDR62 mediates TNFα-dependent JNK activation via TRAF2-MLK3 axis.
Article in Molecular biology of the cell, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 17 citations in OpenAlex.
- Novel treatment-specific causal biomarkers for colorectal cancer by omics integration.NAR genomics and bioinformatics · 2025Article
- [Vitexin-4 ″-Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2025Article
- Gene expression biomarkers differentiate overall survival of colorectal cancer upon targeted therapies.Research square · 2024Article
- Heart Failure Promotes Cancer Progression in an Integrin β1-Dependent Manner.International journal of molecular sciences · 2023Article
- JNK Cascade-Induced Apoptosis-A Unique Role in GqPCR Signaling.International journal of molecular sciences · 2023Review
- Review
- Systematic Analysis of the Oncogenic Role of WDR62 in Human Tumors.Disease markers · 2021Article
- Mitochondrial Protection by PARP Inhibition.International journal of molecular sciences · 2020Review
- c-Jun promotes the survival of H9c2 cells under hypoxia via PTEN/Akt signaling pathway.Journal of physiology and biochemistry · 2019Article
- MEKK3 coordinates with FBW7 to regulate WDR62 stability and neurogenesis.PLoS biology · 2018Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The mitogen-activated protein kinases (MAPKs) regulate a variety of cellular processes. The three main MAPK cascades are the extracellular signal-regulated kinases (ERK), c-Jun N-terminal kinase (JNK), and p38 kinases. A typical MAPK cascade is composed of MAP3K-MAP2K-MAPK kinases that are held by scaffold proteins. Scaffolds function to assemble the protein tier and contribute to the specificity and efficacy of signal transmission. WD repeat domain 62 (WDR62) is a JNK scaffold protein, interacting with JNK, MKK7, and several MAP3Ks. The loss of WDR62 in human leads to microcephaly and pachygyria. Yet the role of WDR62 in cellular function is not fully studied. We used the CRISPR/Cas9 and short hairpin RNA approaches to establish a human breast cancer cell line MDA-MB-231 with WDR62 loss of function and studied the consequence to JNK signaling. In growing cells, WDR62 is responsible for the basal expression of c-Jun. In stressed cells, WDR62 specifically mediates TNFα-dependent JNK activation through the association with both the adaptor protein, TNF receptor-associated factor 2 (TRAF2), and the MAP3K protein, mixed lineage kinase 3. TNFα-dependent JNK activation is mediated by WDR62 in HCT116 and HeLa cell lines as well. MDA-MB-231 WDR62-knockout cells display increased resistance to TNFα-induced cell death. Collectively, WDR62 coordinates the TNFα receptor signaling pathway to JNK activation through association with multiple kinases and the adaptor protein TRAF2.
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