Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0025362 (mental retardation)
 15,878 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neural cell adhesion proteins play important roles in neural development and are involved in various neurological diseases. P0, a major protein in mammalian peripheral myelin, mediates not only homophilic cell adhesion but also neurite outgrowth. The P0 glycopeptide inhibits the cell adhesion, but not the neurite outgrowth. Several point mutations of the P0 gene in human chromosome 1q22-23 were found in Charcot-Marie-Tooth (CMT) disease type 1B and Dejerine-Sottas (DS) disease. PASII/PMP22 and connexin 32 were also reported as target proteins of similar hereditary neuropathies. L1 is a large multifunctional protein involved in cell adhesion, neurite outgrowth, fasciculation, and neuronal cell migration. A short isoform of L1 localizes in non-neuronal cells in contrast to the complete L1 exclusively expressed in neurons. Recently various L1 mutations have been reported in X-linked hydrocephalus, MASA syndrome with mental retardation and spastic paraplegia type 1. Further studies on the mutations and disease phenotypes are important and interesting.
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PMID:Neural cell adhesion proteins and neurological diseases. 770 5

The CC2D1A/Freud-1 gene has recently been linked to non-syndromic mental retardation and a short isoform of mouse Five prime REpressor Under Dual repression binding protein 1 (Freud-1) can repress the serotonin-1A (5-HT1A) receptor gene in rodent cells. In this study, we addressed the expression, localization and regulation of the human 5-HT1A receptor gene by a long isoform of human Freud-1 protein (Freud-1L). We show that human CC2D1A/Freud-1 RNA is expressed in brain and peripheral tissues and encodes short and long isoforms, which differ by an upstream in-frame translational start site. Whereas previous studies identified the short isoform of Freud-1 as the predominant isoform in rodent cells, we demonstrate that the long isoform is more abundant in human cells, especially in the nuclear fraction. The nuclear localization of Freud-1L was enriched upon inhibition of chromosome region maintenance 1/exportin 1-dependent nuclear export, indicating a dynamic regulation of Freud-1 nuclear localization. Consistent with a functional role in the nucleus, human Freud-1L bound specifically to its dual repressor element in the 5-HT1A receptor gene in vitro and repressed transcription from these sites. Importantly, chromatin immunoprecipitation using antibodies specific for human Freud-1L demonstrated that it is bound to the dual repressor element in chromatin, indicating a functional role in regulating the basal expression of the 5-HT1A receptor gene. Taken together, these results indicate that both the short and long isoforms of Freud-1 are expressed, although Freud-1L is the major isoform that regulates the human 5-HT1A receptor gene. Disruption of transcriptional regulation by mutation of Freud-1 may play a role in abnormal brain function leading to mental retardation.
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PMID:The mental retardation gene CC2D1A/Freud-1 encodes a long isoform that binds conserved DNA elements to repress gene transcription. 1771 90

Despite extensive study of heterochromatin, relatively little is known about the mechanisms by which such a structure forms. We show that the Drosophila homologue of the human alpha-thalassemia and mental retardation X-linked protein (dATRX), is important in the formation or maintenance of heterochromatin through modification of position effect variegation. We further show that there are two isoforms of the dATRX protein, the longer of which interacts directly with heterochromatin protein 1 (dHP-1) through a CxVxL motif both in vitro and in vivo. These two proteins co-localise at heterochromatin in a manner dependent on this motif. Consistent with this observation, the long isoform of the dATRX protein localises primarily to the heterochromatin at the chromocentre on salivary gland polytene chromosomes, whereas the short isoform binds to many sites along the chromosome arms. We suggest that the establishment of a regular nucleosomal organisation may be common to heterochromatin and transcriptionally repressed chromatin in other locations, and may require the action of ATP dependent chromatin remodelling factors.
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PMID:The chromatin remodelling factor dATRX is involved in heterochromatin formation. 1846 Nov 25