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Activation of steroid receptors results in global changes of gene expression patterns. Recent studies showed that steroid receptors control only a portion of their target genes directly, by promoter binding. The majority of the changes are indirect, through chromatin rearrangements. The mediators that relay the hormonal signals to large-scale chromatin changes are, however, unknown. We report here that APRIN, a novel hormone-induced nuclear phosphoprotein has the characteristics of a chromatin regulator and may link endocrine pathways to chromatin. We showed earlier that APRIN is involved in the hormonal regulation of proliferative arrest in cancer cells. To investigate its function we cloned and characterized APRIN orthologs and performed homology and expression studies. APRIN is a paralog of the cohesin-associated Pds5 gene lineage and arose by gene-duplication in early vertebrates. The conservation and domain differences we found suggest, however, that APRIN acquired novel chromatin-related functions (e.g. the HMG-like domains in APRIN, the hallmarks of chromatin regulators, are absent in the Pds5 family). Our results suggest that in interphase nuclei APRIN localizes in the euchromatin/heterochromatin interface and we also identified its DNA-binding and nuclear import signal domains. The results indicate that APRIN, in addition to its Pds5 similarity, has the features and localization of a hormone-induced chromatin regulator.
Pubmed ID: 17997301
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Web application to search nucleotide databases using a nucleotide query. Algorithms: blastn, megablast, discontiguous megablast.
View all literature mentionsA sister database to ProSite, is constituted of manually created rules that increase the discriminatory power of PROSITE motifs (generally profiles) by providing additional information about functionally and/or structurally critical amino acids and can automatically generate annotation based on PROSITE motifs in the UniProtKB/Swiss-Prot format. Each ProRule is defined in the UniRule format. In addition to these rules corresponding to a unique PROSITE motif, there are also rules triggered by a specific combination of PROSITE motifs called metamotifs. Metamotifs allow the definition of arrangements of domains separated by spacers of variable size, as well as the anchoring to the N- and/or C-termini and the exclusion of a PROSITE motif. ProRule uses the UniRule format that is common to all types of rules created to annotate UniProtKB/Swiss-Prot, including the HAMAP family rules. Each rule contains information used to provide template based annotation associated with the domain or family detected by the PROSITE motif. ProRule is used to create UniProtKB/Swiss-Prot lines with basic and complex annotation derived from the presence of the domain and of biologically critical amino acids: domain name and boundaries, EC number, function, keywords, associated PROSITE patterns, PTMs, active sites, disulfide bonds, etc.). ProRule contains notably the position of structurally and/or functionally critical amino acid(s), as well as the condition(s) they must fulfil to play their biological role(s). Part of these supplementary data are used by ScanProsite that not only provides the protein sequence matched by a profile, but also information about the relevance of biologically meaningful residues, like active sites, binding sites, post-translational modification sites or disulfide bonds, to help function determination
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