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Beschreibung:
mTOR controls cell growth, in part by regulating p70 S6 kinase alpha (p70alpha) and eukaryotic initiation factor 4E binding protein 1 (4EBP1). Raptor is a 150 kDa mTOR binding protein that also binds 4EBP1 and p70alpha. The binding of Raptor to mTOR is necessary for the mTOR-catalyzed phosphorylation of 4EBP1 in vitro, and it strongly enhances the mTOR kinase activity toward p70alpha. Rapamycin or amino acid withdrawal increases, whereas insulin strongly inhibits, the recovery of 4EBP1 and raptor on 7-methyl-GTP Sepharose. Partial inhibition of raptor expression by RNA interference (RNAi) reduces mTOR-catalyzed 4EBP1 phosphorylation in vitro. RNAi of C. elegans raptor yields an array of phenotypes that closely resemble those produced by inactivation of Ce-TOR. Thus, raptor is an essential scaffold for the mTOR-catalyzed phosphorylation of 4EBP1 and mediates TOR action in vivo.
Beschreibung:
C1orf77, also known as Friend of PRMT1 protein, is a 248 amino acid protein that plays an essential role in the ligand-dependent activation of estrogen receptor target genes. C1orf77 is tightly associated with chromatin and is modified by both asymmetric and symmetric arginine methylation. Depletion of C1orf77 results in almost complete block of estradiol-induced promter occupancy by the estrogen receptor. Also, complete knockdown of C1orf77 mRNA in adult erythroid progenitors stongly induces fetal hemoglobin, suggesting that C1orf77 is a critical modulator of γ-globin gene expression. There are two isoforms of C1orf77 that are produced as a result of alternative splicing events. The gene encoding C1orf77 maps to human chromosome 1, the largest human chromosome spanning about 260 million base pairs and making up 8% of the human genome. There are about 3,000 genes on chromosome 1, and considering the great number of genes there are also a large number of diseases associated with chromosome 1.
Beschreibung:
The Dumpy-30 (DPY-30) protein was first described in C. elegans, in which it is involved in dosage compensation of sex chromosomes. Conserved from yeast to humans, the DPY-30 family is involved in gene expression and chromatin modification, specifically histone methylation. DPY-30 and closely related proteins contain a short motif that is related to the dimerization motif in the regulatory subunit of protein kinase A (PKA), which consists of two ?helices that form a four-helix bundle during dimerization. As a member of the DPY-30 family, DYDC1 (DPY30 domain-containing protein 1), also known as DPY30D1 and RSD9, is a 177 amino acid protein that binds to Endophilin III and plays a crucial role during acrosome biogenesis. DYDC1 is specifically expressed in brain and testis and accumulates in the acrosome area during spermatogenesis. Knockdown of DYDC1 mRNA results in disruption of acrosome formation and spermatid differentiation.
Beschreibung:
Fragile X syndrome is the most frequent form of inherited mental retardation and is the result of transcriptional silencing of the FMR1 gene on the X chromosome. The FMR1 gene contains a distinct CpG dinucleotide repeat located in the 5' untranslated region of the gene. In fragile X syndrome this tandem repeat is substantially amplified and subjected to extensive methylation and enhanced transcriptional silencing. The FMR1 protein (or FMRP) is an RNA-binding protein that associates with polyribosomes and is a likely component of a messenger ribonuclear protein (mRNP) particle. It contains several features that are characteristics of RNA-binding proteins, including two hnRNPK homology (KH) domains and an RGG amino acid motif (RGG box). FMR1 localizes to both the nucleus and the cytoplasm and can also interact with two fragile X syndrome related factors, FXR1 and FXR2, which form heterodimers through their N-terminal coiled-coil domains. Since FMR1 contains both a nuclear localization signal and a nuclear export signal it is also implicated in the nucleocytoplasmic transport of mRNAs.
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