The function of the Aristaless-related homeobox (Arx) gene product as a transcriptional repressor is diminished by mutations associated with X-linked mental retardation (XLMR).
The Aristaless-related homeobox (Arx) is mutated in patients with X-linked mental retardation and a range of other neurological diseases. The molecular consequences of these mutations are unclear. Here, we show that two disease-associated mutations disrupt the function of Arx as a transcriptional repressor. We found that Arx contains two independent repression domains: an N-terminal octapeptide motif/engrailed homology domain and a novel domain located in the C-terminus. The octapeptide motif functions through interaction with members of the Groucho family of co-repressors. The C-terminal domain functions through interaction with C-terminal binding protein (CtBP).
Graduate Program in Molecular, Cellular, and Developmental Biology, School of Biological Sciences, The Ohio State University, Columbus, OH, USA.
Amy N
AN
Fullenkamp
Heithem M
HM
El-Hodiri
D000429:Alcohol Oxidoreductases / Q000235:genetics / Q000378:metabolism; D020816:Amino Acid Motifs; D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D056970:Co-Repressor Proteins; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D038901:X-Linked Intellectual Disability / Q000235:genetics*; D009154:Mutation; D017434:Protein Structure, Tertiary / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic; D014981:Xenopus; D029867:Xenopus Proteins / Q000235:genetics* / Q000378:metabolism
D056970:Co-Repressor Proteins; D004268:DNA-Binding Proteins; D012097:Repressor Proteins; C523700:TLE4 protein, Xenopus; D014157:Transcription Factors; D029867:Xenopus Proteins; C502721:aristaless-related homeobox protein, Xenopus; D000429:Alcohol Oxidoreductases; C096794:C-terminal binding protein