Linked Life Data

16332686

Source:http://linkedlifedata.com/resource/pubmed/id/16332686

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2006-2-13
pubmed:abstractText
FE65 has been described as an adaptor protein; its partners include the beta-amyloid precursor protein (APP) and Tip60 (a histone acetyltransferase). Recent evidence suggests that APP may function in a nuclear signaling pathway via formation of APP-FE65-Tip60 complexes. The evidence is largely based on experiments in which APP/Tip60 is fused to the DNA binding domain of a yeast transcriptional factor Gal4 (Gal4DB) that can activate a reporter gene only when FE65 is coexpressed. One interpretation of published experiments has not yet been tested; however, there is the possibility that FE65 itself is the dominant transcriptional activator, whereas APP and Tip60 serve merely as positive/negative modulators or bridges for connecting FE65 to Gal4DB. To test this possibility, we fused Gal4DB directly to either end of FE65 and assessed their nuclear signaling in the presence or absence of exogenous APP/Tip60 or after knockdown of endogenous APP/Tip60. We found that FE65-Gal4DB by itself was able to trigger robust reporter activities. Increasing levels of APP could not further augment the reporter activity, but knocking down endogenous APP or interrupting FE65-APP binding reduced the signaling by up to 2-fold. The magnitudes of the reporter activities did not correlate with relative FE65 affinities for APP. Both overexpression and knockdown experiments showed that Tip60 plays a negative role. The results are consistent with the notion that FE65 is the key agent of Gal4DB-mediated transcriptional transactivation, whereas Tip60 is an FE65-associated repressor. Although APP may have modest stimulating effects, apparently there is no absolute requirement for that molecule for the nuclear signaling pathway.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/APBB1 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Acetyltransferases, http://linkedlifedata.com/resource/pubmed/chemical/Amyloid beta-Protein Precursor, http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins, http://linkedlifedata.com/resource/pubmed/chemical/GAL4 protein, S cerevisiae, http://linkedlifedata.com/resource/pubmed/chemical/Histone Acetyltransferases, http://linkedlifedata.com/resource/pubmed/chemical/KAT5 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Luciferases, http://linkedlifedata.com/resource/pubmed/chemical/Nerve Tissue Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Saccharomyces cerevisiae Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
17
pubmed:volume
281
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4207-14
pubmed:dateRevised
2011-9-28
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
A dominant role for FE65 (APBB1) in nuclear signaling.
pubmed:affiliation
Department of Pathology, the University of Washington, Seattle, 98195, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural