ArticleMolecular medicine reports2020
KCTD1 mutants in scalp‑ear‑nipple syndrome and AP‑2α P59A in Char syndrome reciprocally abrogate their interactions, but can regulate Wnt/β‑catenin signaling.
Article in Molecular medicine reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 17 citations in OpenAlex.
- A Global Analysis of the Complex Structural Organization of KCTD Proteins and Their Functional Implications.International journal of molecular sciences · 2026Review
- KCTD1/KCTD15-Mediated Repression of AP-2α/AP-2β Is Required for Proper Skin Appendage Development and Epidermal Homeostasis.The Journal of investigative dermatology · 2026Article
- Article
- Advances in prenatal ultrasound diagnosis of fetal tympanic ring anomalies.Frontiers in medicine · 2026Review
- Exosomes delivering miR-129-5p combined with sorafenib ameliorate hepatocellular carcinoma progression via the KCTD1/HIF-1α/VEGF pathway.Cellular oncology (Dordrecht, Netherlands) · 2025Article
- Aplasia Cutis Congenita Pathomechanisms Reveal Key Regulators of Skin and Skin Appendage Morphogenesis.The Journal of investigative dermatology · 2024Review
- A BTB extension and ion-binding domain contribute to the pentameric structure and TFAP2A binding of KCTD1.Structure (London, England : 1993) · 2024Article
- AP-2α/AP-2β Transcription Factors Are Key Regulators of Epidermal Homeostasis.The Journal of investigative dermatology · 2024Article
- Genetic Variants inInternational journal of molecular sciences · 2024Article
- Genomic landscape of diploid and aneuploid microsatellite stable early onset colorectal cancer.Scientific reports · 2024Article
- BTB domain mutations perturbing KCTD15 oligomerisation cause a distinctive frontonasal dysplasia syndrome.Journal of medical genetics · 2024Article
- KCTD1/KCTD15 complexes control ectodermal and neural crest cell functions, and their impairment causes aplasia cutis.The Journal of clinical investigation · 2023Article
- AP-2α/AP-2β transcription factors are key regulators of epidermal homeostasis.bioRxiv : the preprint server for biology · 2023Article
- Article
- Identification ofDiagnostics (Basel, Switzerland) · 2022Article
- Loss-of-function, gain-of-function and dominant-negative mutations have profoundly different effects on protein structure.Nature communications · 2022Article
- Article
- Therapeutic Response-Based Reclassification of Multiple Tumor Subtypes Reveals Intrinsic Molecular Concordance of Therapy Across Histologically Disparate Cancers.Frontiers in cell and developmental biology · 2021Article
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Potassium‑channel tetramerization-domain-containing 1 (KCTD1) mutations are reported to result in scalp‑ear‑nipple syndrome. These mutations occur in the conserved broad‑complex, tramtrack and bric a brac domain, which is associated with inhibited transcriptional activity. However, the mechanisms of KCTD1 mutants have not previously been elucidated; thus, the present study aimed to investigate whether KCTD1 mutants affect their interaction with transcription factor AP‑2α and their regulation of the Wnt pathway. Results from the present study demonstrated that none of the ten KCTD1 mutants had an inhibitory effect on the transcriptional activity of AP‑2α. Co‑immunoprecipitation assays demonstrated that certain mutants exhibited changeable localization compared with the nuclear localization of wild‑type KCTD1, but no KCTD1 mutant interacted with AP‑2α. Almost all KCTD1 mutants, except KCTD1 A30E and H33Q, exhibited differential inhibitory effects on regulating TOPFLASH luciferase reporter activity. In addition, the interaction region of KCTD1 to the PY motif (amino acids 59‑62) in AP‑2α was identified. KCTD1 exhibited no suppressive effects on the transcriptional activity of the AP‑2α P59A mutant, resulting in Char syndrome, a genetic disorder characterized by a distinctive facial appearance, heart defect and hand abnormalities, by altered protein cellular localization that abolished protein interactions. However, the P59A, P60A, P61R and 4A AP‑2α mutants inhibited TOPFLASH reporter activity. Moreover, AP‑2α and KCTD1 inhibited β‑catenin expression levels and SW480 cell viability. The present study thus identified a putative mechanism of disease‑related KCTD1 mutants and AP‑2α mutants by disrupting their interaction with the wildtype proteins AP‑2α and KCTD1 and influencing the regulation of the Wnt/β‑catenin pathway.
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