Transcript What is so memorable about CREBBP?

What is so memorable about
CREBBP?
(RSTS; RTS, CBP CBP/MOZ FUSION GENE, CREB-binding protein)
Where is it found?
What exactly does “BP” mean
• Binding protien
• What is a coactivator and what is its role?
• Does it perform one function (interaction)
or does it perform many? pg224 of book
•
http://www.ebi.ac.uk/intact/search/do/search?searchString=EBI81215&filter=ac&searchClass=Protein&view=partner&filter=ac
What is its function and where is it found? Gene Ontology
Ontology
Molecular Function
Gene
Ontologies
Biological Process
Cellular Component
Annotation
Evidence
Source
Histone acetyltransferase activity
IEA
GOA/IPI
Signal transducer activity
Transcription coactivator activity
Transcription coactivator activity
Protein binding
Transcription factor activity
Transferase activity
Zinc ion binding
Regulation of transcription, DNA-dependent
Regulation of transcription, DNA-dependent
Response to hypoxia
Homeostasis
Signal transduction
Protein complex assembly
Cytoplasm
Nucleus
Nucleus
TAS
IEA
IPI
IPI
TAS
IEA
IEA
IEA
TAS
TAS
NAS
NAS
TAS
TAS
IEA
TAS
GOA/IPI
GOA/IPI
GOA/IPI
GOA/IPI
GOA/IPI
GOA/IPI
GOA/IPI
GOA/IPI
GOA/IPI
GOA/IPI
GOA/IPI
GOA/IPI
GOA/IPI
GOA/IPI
GOA/IPI
GOA/IPI
Normalized
Expression (%)
Cluster Clones :
Tissue clones
posterior tongue (pooled):
22.02
2:473
Brain:
10.61
1:491
liposarcoma:
5.31
1:980
lymph:
3.84
15:20369
Trabecular meshwork:
3.65
2:2854
metastatic prostate bone lesion:
3.24
2:3214
fibrotheoma:
2.51
3:6234
prostata:
salivary gland:
myeloid cells, 18 pooled CML cases, BCR/ABL rearrangement positive, includes both chronic phase
and myeloid blast crisis:
2.21
2.07
1:2355
1:2521
Tissue
Normalized
expression
distribution
for tissue
type
Top ten
2.01
1:2589
What makes up the coding
sequence?
It is made of 32 exons and 31 introns. The
mRNA itself is 8.7 kb, 7.3 of that is
coding!
Enough about its genome, lets talk
protein!
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The protein is made of 2442 amino acids
and is 265 kDa!
That’s nice, but what does it look like?
Seven Different Domains
Bromodomain
KIX
Zinc finger ZZ type
Two Domains of unknown
functions (interact with
other pfams
TAZ zinc
finger
Creb
binding
So now that I know what its made of
and where its found…. What does it
do?
• Mediates cAMP-gene regulation by
binding specifically to phosphorylated
CREB protein. CREBBP, as coactivator,
augments the activity of phosphorylated
CREB to activate transcription of cAMPresponsive genes.
• What do we know about cAMP and
memory? pg.223
Sounds nice, but what does that
have to do with memory?
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http://www.dnai.org/text/mediashowcase/index2.html?id=483
CREB turns on other genes to store in long term memory.
Switched on to create new connections between nerve cells
Turning off and on genes by the act of remembering.
In other words, CREB is a gene that mediates long-term memory. It
acts as a master gene that turns on other genes, assisted by
CREBBP
• Evidence for this function- studies on CREBBP transgenic mice
suggests that competition for CBP plays an important role in regulating
gene expression during cell growth. CREBBP and p300 function as
transcriptional coactivators in the regulation of gene expression through
various signal transduction pathways
Diseases associated with CREBBP
• Rubinstein-Taybi
syndrome
•
Result of germline mutation of
CREBBP
• myeloid leukemias
• MLL translocations involving the
CREBBP gene have primarily been
reported in treatment-related acute
myeloid lukemia after
chemotherapy for other primary
malignancies using topoisomerase
II inhibitors.
References
Ridley, Matt. "Chromosome 16, Memory." Genome, The Autobiography of a species in
23 Chapters. New York: Harper Perennial, 1999. 219-230.
http://www.dsi.univ-paris5.fr/genatlas/fiche.php?symbol=CREBBP (slide 2,6)
http://atlasgeneticsoncology.org/Genes/CBPID42.html (slide 10)
http://genome-www5.stanford.edu/cgibin/source/sourceResult?criteria=CREBBP&choice=Gene&option=Symbol&organism=Hs
(slide 4, 8)
http://www.ihop-net.org/UniPub/iHOP/gismo/87420.html (slide and 9)
http://www.ncbi.nlm.nih.gov/genome/guide/human/ (slide 1)
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=gene&cmd=Retrieve&dopt=full_report&list_uid
s=1387 (slide 5)
http://www.ebi.ac.uk/intact/search/do/search?searchString=EBI81215&filter=ac&searchClass=Protein&view=partner&filter=ac (slide 3)
http://www.sanger.ac.uk/cgi-bin/Pfam/qquerypfam.pl?terms=crebbp (slide 7)