Linked Life Data

12466963

Source:http://linkedlifedata.com/resource/pubmed/id/12466963

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
55
pubmed:dateCreated
2002-12-5
pubmed:databankReference
pubmed:abstractText
To study the regulation of acetylcholinesterase (AChE) gene expression in human brain tumors, 3' splice variants of AChE mRNA and potentially relevant transcription factor mRNAs were labeled in primary astrocytomas and melanomas. AChE-S and AChE-R mRNA, as well as Runx1/AML1 mRNA accumulated in astrocytomas in correlation with tumor aggressiveness, but neither HNF3beta nor c-fos mRNA was observed in melanoma and astrocytomas. Immunohistochemistry demonstrated nuclear Runx1/AML1 and cellular AChE-S and AChE-R in melanomas, however, only AChE-S, and not the secreted AChE-R variant, was retained in astrocyte tumor cells. Runx1/AML1 revealed weak linkage with ACHE promoter sequences, yet enhanced ACHE gene expression in co-transfected COS1 cells. The p300 co-activator and the ACHE promoter's distal enhancer facilitated this effect, which was independent of much of the Runx1/AML1 trans-activation domain. Surprisingly, GASP, a fusion product of green fluorescence protein (GFP) and ASP(67), a peptide composed of the 67 C-terminal amino acid residues of AChE-S, localized to COS1 cell nuclei. However, GARP, the corresponding fusion product of GFP with a peptide having the 51 C-terminal residues of AChE-E or GFP alone, remained cytoplasmic. Runx1/AML1 exhibited improved nuclear retention in GASP-expressing COS1 cells, suggesting modulated nuclear localization processes. Together, these findings reveal brain tumor-specific regulation of both expression and cellular retention of variant ACHE gene products.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0950-9232
pubmed:author
pubmed:issnType
Print
pubmed:day
5
pubmed:volume
21
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
8428-41
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:12466963-Acetylcholinesterase, pubmed-meshheading:12466963-Alternative Splicing, pubmed-meshheading:12466963-Amino Acid Sequence, pubmed-meshheading:12466963-Astrocytoma, pubmed-meshheading:12466963-Base Sequence, pubmed-meshheading:12466963-Brain Neoplasms, pubmed-meshheading:12466963-Gene Expression Regulation, Enzymologic, pubmed-meshheading:12466963-Gene Expression Regulation, Neoplastic, pubmed-meshheading:12466963-Genetic Variation, pubmed-meshheading:12466963-Green Fluorescent Proteins, pubmed-meshheading:12466963-Humans, pubmed-meshheading:12466963-Luminescent Proteins, pubmed-meshheading:12466963-Molecular Sequence Data, pubmed-meshheading:12466963-Promoter Regions, Genetic, pubmed-meshheading:12466963-RNA, Messenger, pubmed-meshheading:12466963-Recombinant Fusion Proteins
pubmed:year
2002
pubmed:articleTitle
Complex regulation of acetylcholinesterase gene expression in human brain tumors.
pubmed:affiliation
Department of Biological Chemistry, The Institute of Life Sciences, The Hebrew University of Jerusalem, Israel 91904.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't