|
|
|
Ctbp2 should also be
considered a high priority biological candidate gene responsible for
modulating App expression levels. The
C-terminal binding protein 2 is a transcriptional co-repressor also
known as Ribeye. The gene produces two
transcripts encoding distinct proteins. The short form is a transcriptional
repressor that binds a Pro-X-Asp-Leu-Ser peptide motif common to adenoviral
oncoprotein E1a and a related motif in BKLF. This short form also interacts with several transcription factors
including EVI1, ZFPM1, and
ZFHX1A (aka TCF8, deltaEF1). The longer isoform is a major component
of specialized synapses in photoreceptors. Both proteins contain a NAD+
binding domain similar to NAD+-dependent 2-hydroxyacid dehydrogenases.
|
|
|
|
Notes:
|
|
1. To find out more about
CTBP2 protein and the Ctbp2 gene, link to iHOP at
http://www.pdg.cnb.uam.es/UniPub/iHOP/ and type in CTBP2
|
|
Try Arrowsmith at
http://arrowsmith.psych.uic.edu/cgi-test/arrowsmith_uic/pubsmith.cgi
|
|
2. Both APP and CTBP2 are
involved in oxidoreducatase activity or Notch signalling. To estabilish this
common gene ontology visit NCBI
http://www.ncbi.nih.gov/entrez/query.fcgi?db=gene and enter each gene symbol.
|
|
3. You can get intersting
hints regarding Ctbp2 expression partners by examining the genetic
correlations between Ctbp2 probe set 1422887_a_at and all other transcripts
on the M430 Affymetrix array. Use the Striatum data set because we already
know from previous work (the previous slide) that this gene is a cis
QTL. You should be able to show
that Ctbp2 and Notch3 have antagonistic expression patterns in striatum. The
negative genetic correlation with E2f4 is even stronger. The transcript also
has a high positive genetic correlation with Rdh14. Of particualr interest
with respect to APP protein processing, Ctbp2 covaries positiviely with
Bace2 (the transcript of the beta site APP-cleaving enzyme 2).
|
|
|
|
|