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)

We previously identified and purified a human ATP-dependent chromatin remodeling complex with similarity to the Saccharomyces cerevisiae INO80 complex (Jin, J., Cai, Y., Yao, T., Gottschalk, A. J., Florens, L., Swanson, S. K., Gutierrez, J. L., Coleman, M. K., Workman, J. L., Mushegian, A., Washburn, M. P., Conaway, R. C., and Conaway, J. W. (2005) J. Biol. Chem. 280, 41207-41212) and demonstrated that it is composed of (i) a Snf2 family ATPase (hIno80) related in sequence to the S. cerevisiae Ino80 ATPase; (ii) seven additional evolutionarily conserved subunits orthologous to yeast INO80 complex subunits; and (iii) six apparently metazoan-specific subunits. In this report, we present evidence that the human INO80 complex is composed of three modules that assemble with three distinct domains of the hIno80 ATPase. These modules include (i) one that is composed of the N terminus of the hIno80 protein and all of the metazoan-specific subunits and is not required for ATP-dependent nucleosome remodeling; (ii) a second that is composed of the hIno80 Snf2-like ATPase/helicase and helicase-SANT-associated/post-HSA (HSA/PTH) domain, the actin-related proteins Arp4 and Arp8, and the GLI-Kruppel family transcription factor YY1; and (iii) a third that is composed of the hIno80 Snf2 ATPase domain, the Ies2 and Ies6 proteins, the AAA(+) ATPases Tip49a and Tip49b, and the actin-related protein Arp5. Through purification and characterization of hINO80 complex subassemblies, we demonstrate that ATP-dependent nucleosome remodeling by the hINO80 complex is catalyzed by a core complex comprising the hIno80 protein HSA/PTH and Snf2 ATPase domains acting in concert with YY1 and the complete set of its evolutionarily conserved subunits. Taken together, our findings shed new light on the structure and function of the INO80 chromatin-remodeling complex.
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PMID:Subunit organization of the human INO80 chromatin remodeling complex: an evolutionarily conserved core complex catalyzes ATP-dependent nucleosome remodeling. 2130 10

Esophageal squamous cell carcinoma (ESCC) ranks among the five most common cancers in China and has a five-year survival rate of less than 15%. The transcription factor ATPase-family AAA-domain-containing protein 2 (ATAD2) has potential as a therapeutic target in various tumors, and microarray-based gene expression profiling reveals dysregulation of ATAD2 specifically in ESCC. Here we investigated whether ATAD2 could mediate a regulation of cancer stem cell (CSC) biological functions in ESCC. Immunohistochemical staining, reverse transcription quantitative polymerase chain reaction, and Western blot assays all revealed upregulation of ATAD2 in ESCC tissues and cell lines, which furthermore correlated with progression of ESCC. In loss-of-function experiments, silencing of ATAD2 inhibited activation of the Hedgehog signaling pathway, as indicated by reduced expression of glioma-associated oncogene family zinc finger 1 (Gli1), smoothened frizzled class receptor (SMO), and patched 1 (PTCH1). Investigations with 5-ethynyl-2'-deoxyuridine (EdU), Transwell assay, scratch test, flow cytometry, and colony formation assay showed that silencing of ATAD2 or inhibiting the Hedgehog signaling decreased the proliferation, invasion, and migration abilities along with colony formation, but elevated the apoptosis rate of CSCs. Furthermore, in vivo experiments validated the suppressive effect of siRNA-mediated ATAD2 silencing on tumor growth in nude mice. Thus, downregulation of ATAD2 can seemingly restrain the malignant phenotypes of ESCC cells through inhibition of the Hedgehog signaling pathway.
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PMID:Downregulation of AAA-domain-containing protein 2 restrains cancer stem cell properties in esophageal squamous cell carcinoma via blockade of the Hedgehog signaling pathway. 3174 29