Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0162871 (abdominal aortic aneurysm)
 8,664 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Centromeres mediate chromosome segregation and are defined by the centromere-specific histone H3 variant (CenH3)/centromere protein A (CENP-A). Removal of CenH3 from centromeres is a general property of terminally differentiated cells, and the persistence of CenH3 increases the risk of diseases such as cancer. However, active mechanisms of centromere disassembly are unknown. Nondividing Arabidopsis pollen vegetative cells, which transport engulfed sperm by extended tip growth, undergo loss of CenH3; centromeric heterochromatin decondensation; and bulk activation of silent rRNA genes, accompanied by their translocation into the nucleolus. Here, we show that these processes are blocked by mutations in the evolutionarily conserved AAA-ATPase molecular chaperone, CDC48A, homologous to yeast Cdc48 and human p97 proteins, both of which are implicated in ubiquitin/small ubiquitin-like modifier (SUMO)-targeted protein degradation. We demonstrate that CDC48A physically associates with its heterodimeric cofactor UFD1-NPL4, known to bind ubiquitin and SUMO, as well as with SUMO1-modified CenH3 and mutations in NPL4 phenocopy cdc48a mutations. In WT vegetative cell nuclei, genetically unlinked ribosomal DNA (rDNA) loci are uniquely clustered together within the nucleolus and all major rRNA gene variants, including those rDNA variants silenced in leaves, are transcribed. In cdc48a mutant vegetative cell nuclei, however, these rDNA loci frequently colocalized with condensed centromeric heterochromatin at the external periphery of the nucleolus. Our results indicate that the CDC48A(NPL4) complex actively removes sumoylated CenH3 from centromeres and disrupts centromeric heterochromatin to release bulk rRNA genes into the nucleolus for ribosome production, which fuels single nucleus-driven pollen tube growth and is essential for plant reproduction.
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PMID:The AAA-ATPase molecular chaperone Cdc48/p97 disassembles sumoylated centromeres, decondenses heterochromatin, and activates ribosomal RNA genes. 2534 31

Abdominal aortic aneurysm (AAA) is one of the most significant causes of morbidity and mortality in populations aged >65 years worldwide. However, the underlying mechanisms of AAA based on the competitive endogenous RNA (ceRNA) hypothesis have remained elusive. In the present study, differently expressed long non-coding RNA (lncRNA)-microRNA (miRNA)-mRNA networks in AAA were constructed by analyzing public datasets, including GSE7084, GSE24194 from rats and that of a previous study. A total of 1,219 mRNAs, 2,093 lncRNAs and 57 miRNAs were identified to differently express in AAA. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were performed to explore the potential roles of differently expressed lncRNAs based on their regulating mRNAs. Based on the ceRNA hypothesis, lncRNA-miRNA-mRNA networks in AAA were, for the first time, constructed at a system-wide level. The present study identified 5 upregulated lncRNAs [nuclear paraspeckle assembly transcript 1, cyclin-dependent kinase inhibitor 2B antisense RNA 1, small Cajal body-specific RNA 10, AC005224.4 and SUMO1/sentrin/SMT3-specific peptidase 3-eukaryotic translation initiation factor 4A1] and the downregulated zinc ribbon domain containing 1 antisense RNA 1 as key lncRNAs in ceRNA networks. To the best of our knowledge, the present study was the first to screen ceRNA networks in AAA. In addition, key lncRNA-mRNA-biological processes analysis indicated that these key lncRNAs were involved in regulating signal transduction, protein amino acid phosphorylation, immune response, transcription, development and cell differentiation. The present study provides novel clues to explore the molecular mechanisms of AAA progression in terms of lncRNA implication.
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PMID:Construction of lncRNA-miRNA-mRNA networks reveals functional lncRNAs in abdominal aortic aneurysm. 3034 76