Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0013421 (dystonia)
 8,418 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Aristaless-related homeobox gene (ARX) is an important paired-type homeobox gene involved in the development of human brain. The ARX gene mutations are a significant contributor to various forms of X-chromosome-linked mental retardation with and without additional features including epilepsy, lissencephaly with abnormal genitalia, hand dystonia or autism. Here we demonstrate that the human ARX protein is a potent transcriptional repressor, which binds to Groucho/transducin-like enhancer of split (TLE) co-factor proteins and the TLE1 in particular through its octapeptide (Engrailed homology repressor domain (eh-1) homology) domain. We show that the transcription repression activity of ARX is modulated by two strong repression domains, one located within the octapeptide domain and the second in the region of the polyalanine tract 4, and one activator domain, the aristaless domain. Importantly, we show that the transcription repression activity of ARX is affected by various naturally occurring mutations. The introduction of the c.98T>C (p.L33P) mutation results in the lack of binding to TLE1 protein and relaxed transcription repression. The introduction of the two most frequent ARX polyalanine tract expansion mutations increases the repression activity in a manner dependent on the number of extra alanines. Interestingly, deletions of alanine residues within polyalanine tracts 1 and 2 show low or no effect. In summary we demonstrate that the ARX protein is a strong transcription repressor, we identify novel ARX interacting proteins (TLE) and offer an explanation of a molecular pathogenesis of some ARX mutations, including the most frequent ARX mutations, the polyalanine tract expansion mutations, c.304ins(GCG)7 and c.428_451dup.
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PMID:Aristaless-related homeobox gene, the gene responsible for West syndrome and related disorders, is a Groucho/transducin-like enhancer of split dependent transcriptional repressor. 1733 56

B-cell receptor-associated protein 31 (Bap31) is a three trans-membrane protein of the endoplasmic reticulum (ER). Patients who have loss of function of Bap31 suffered from X-linked syndrome, such as motor and intellectual disabilities, dystonia, and sensorineural deafness. However, the underlying mechanism of Bap31 on X-linked syndrome remains unclear. Here, we found that a total of 21 proteins (9 up-regulated and 12 down-regulated proteins) related with X-linked syndrome were screened from shRNA-Bap31 transfected cells with the isobaric tags for relative and absolute quantification (iTRAQ) technique. One gene with the greatest change trend, monoamine oxidase A (MAOA), was identified. MAOA expression was up-regulated by Bap31 knockdown. However, Bap31 did not affect the ubiquitination degradation of MAOA protein. Of note, Bap31 selectively regulated the expression of cell division cycle associated 7-like (R1/RAM2/CDCA7L/JPO2, a transcriptional repressor of MAOA) and the binding activity of R1 with MAOA promoter, thereby affecting MAOA expression. This study demonstrates the molecular mechanisms of Bap31 in MAOA via R1 and supports the potential function of Bap31 on X-linked syndrome.
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PMID:B-Cell Receptor-Associated Protein 31 Negatively Regulates the Expression of Monoamine Oxidase A Via R1. 3242 68