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.

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. 2020 Nov;22(5):3895-3903 Authors: Hu L, Chen L, Yang L, Ye Z, Huang W, Li X, Liu Q, Qiu J, Ding X 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 suppr...
Source: Molecular Medicine Reports - Category: Molecular Biology Tags: Mol Med Rep Source Type: research