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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

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What is so memorable about CREBBP?

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  1. What is so memorable about CREBBP? (RSTS; RTS, CBP CBP/MOZ FUSION GENE, CREB-binding protein)

  2. Where is it found?

  3. 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

  4. What is its function and where is it found? Gene Ontology

  5. 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!

  6. 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?

  7. Seven Different Domains Bromodomain Zinc finger ZZ type TAZ zinc finger KIX Two Domains of unknown functions (interact with other pfams Creb binding

  8. 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

  9. 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

  10. 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.

  11. References Ridley, Matt. "Chromosome 16, Memory." Genome, The Autobiography of a species in23 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)

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