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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

  • Authors:
    • Lingyu Hu
    • Li Chen
    • Liu Yang
    • Zi Ye
    • Wenhuan Huang
    • Xinxin Li
    • Qing Liu
    • Junlu Qiu
    • Xiaofeng Ding
  • View Affiliations / Copyright

    Affiliations: Department of Obstetrics and Gynecology, Third Xiangya Hospital of The Central South University, Changsha, Hunan 410013, P.R. China, Key Laboratory of Protein Chemistry and Development Biology of State Education Ministry of China, College of Life Science, Hunan Normal University, Changsha, Hunan 410081, P.R. China, Yali High School of Changsha, Changsha, Hunan 410007, P.R. China
    Copyright: © Hu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 3895-3903
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    Published online on: August 24, 2020
       https://doi.org/10.3892/mmr.2020.11457
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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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Copy and paste a formatted citation
Spandidos Publications style
Hu L, Chen L, Yang L, Ye Z, Huang W, Li X, Liu Q, Qiu J and Ding X: 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. Mol Med Rep 22: 3895-3903, 2020.
APA
Hu, L., Chen, L., Yang, L., Ye, Z., Huang, W., Li, X. ... Ding, X. (2020). 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. Molecular Medicine Reports, 22, 3895-3903. https://doi.org/10.3892/mmr.2020.11457
MLA
Hu, L., Chen, L., Yang, L., Ye, Z., Huang, W., Li, X., Liu, Q., Qiu, J., Ding, X."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". Molecular Medicine Reports 22.5 (2020): 3895-3903.
Chicago
Hu, L., Chen, L., Yang, L., Ye, Z., Huang, W., Li, X., Liu, Q., Qiu, J., Ding, X."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". Molecular Medicine Reports 22, no. 5 (2020): 3895-3903. https://doi.org/10.3892/mmr.2020.11457
Copy and paste a formatted citation
x
Spandidos Publications style
Hu L, Chen L, Yang L, Ye Z, Huang W, Li X, Liu Q, Qiu J and Ding X: 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. Mol Med Rep 22: 3895-3903, 2020.
APA
Hu, L., Chen, L., Yang, L., Ye, Z., Huang, W., Li, X. ... Ding, X. (2020). 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. Molecular Medicine Reports, 22, 3895-3903. https://doi.org/10.3892/mmr.2020.11457
MLA
Hu, L., Chen, L., Yang, L., Ye, Z., Huang, W., Li, X., Liu, Q., Qiu, J., Ding, X."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". Molecular Medicine Reports 22.5 (2020): 3895-3903.
Chicago
Hu, L., Chen, L., Yang, L., Ye, Z., Huang, W., Li, X., Liu, Q., Qiu, J., Ding, X."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". Molecular Medicine Reports 22, no. 5 (2020): 3895-3903. https://doi.org/10.3892/mmr.2020.11457
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