what is so memorable about crebbp?
DESCRIPTION
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 - PowerPoint PPT PresentationTRANSCRIPT
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=EBI-81215&filter=ac&searchClass=Protein&view=partner&filter=ac
What is its function and where is it found? Gene Ontology
Gene Ontologies
Normalized expression distribution for tissue type Top ten
Ontology Annotation Evidence Source
Molecular Function
Histone acetyltransferase activity IEA GOA/IPI
Signal transducer activity TAS GOA/IPI
Transcription coactivator activity IEA GOA/IPI
Transcription coactivator activity IPI GOA/IPI
Protein binding IPI GOA/IPI
Transcription factor activity TAS GOA/IPI
Transferase activity IEA GOA/IPI
Zinc ion binding IEA GOA/IPI
Biological Process
Regulation of transcription, DNA-dependent IEA GOA/IPI
Regulation of transcription, DNA-dependent TAS GOA/IPI
Response to hypoxia TAS GOA/IPI
Homeostasis NAS GOA/IPI
Signal transduction NAS GOA/IPI
Protein complex assembly TAS GOA/IPI
Cellular ComponentCytoplasm TAS GOA/IPI
Nucleus IEA GOA/IPI
Nucleus TAS GOA/IPI
TissueNormalized
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: 2.21 1:2355
salivary gland: 2.07 1:2521
myeloid cells, 18 pooled CML cases, BCR/ABL rearrangement positive, includes both chronic phase and myeloid blast crisis:
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!
• The protein is made of 2442 amino acids and is 265 kDa!
• That’s nice, but what does it look like?
Seven Different Domains
BromodomainZinc finger ZZ type TAZ zinc
finger
KIX Two Domains of unknown functions (interact with other pfams
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 cAMP-responsive genes.
• What do we know about cAMP and memory? pg.223
Sounds nice, but what does that have to do with memory?
• 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.
ReferencesRidley, 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/cgi-bin/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_uids=1387 (slide 5)
http://www.ebi.ac.uk/intact/search/do/search?searchString=EBI-81215&filter=ac&searchClass=Protein&view=partner&filter=ac (slide 3)
http://www.sanger.ac.uk/cgi-bin/Pfam/qquerypfam.pl?terms=crebbp (slide 7)