| Entity | t(8;16)(p11;p13)/M4 ANLL --> MOZ/CBP |
| Disease | Acute non lymphocytic leukemia (ANLL) and treatment related ANLL (t-ANLL). |
| Prognosis | Poor: remission is obtained in half cases; survival is often less than 1yr. |
| Cytogenetics | +8 as an additional anomalies in half cases. |
| Hybrid/Mutated Gene | 5' MOZ - 3' CBP. |
| Abnormal Protein | N-term finger motifs and acetyl transferase from MOZ fused to most of CBP, with a breakpoint in 5' of the CREB binding domain of CBP. |
| | |
| Entity | t(10;16)(q22;p13)/M4 ANLL --> MYST4/CBP |
| Disease | Acute myeloid leukaemia (AML) M4/M5a and therapy-related myelodysplastic syndromes (MDS). Only 4 cases described. |
| Prognosis | Poor, bad response to chemotherapy. |
| Hybrid/Mutated Gene | 5' MYST4 - 3' CBP. |
| Abnormal Protein | In-frame fusion between MYST4 exon 17 and CREBBP exon 3. Variants fusing MYST4 exon 16 and CREBBP exon 5; MYST4 exon 17 and CREBBP exon 7 have been also described. CREBBP-MYST4 transcripts have been detected. |
| | |
| Entity | t(11;16)(q23;p13)/t-ANLL --> MLL/CBP |
| Disease | Therapy related ANLL (t-ANLL); should be very close to the t(11;22)(q23;q13). |
| Prognosis | Likely to be poor. |
| Hybrid/Mutated Gene | 5' MLL - 3'CBP. |
| Abnormal Protein | N-term AT hook and DNA methyltransferase from MLL fused to most of CBP; variable brakpoint in CBP: either 5' to the CREB binding domain (like in the t(8;16)), or just upstream the bromodomain. |
| | |
| Entity | Rubinstein-Taybi syndrome |
| Note | Due to CBP haploinsufficiency. |
| Disease | Rare autosomal dominant congenital disorder characterized by postnatal growth retardation and psychomotor developmental delay, skeletal anomalies (broad and duplicated distal phalanges of thumbs and halluces are a landmark sign) and specific facial dysmorphisms. The latter include down-slanted palpebral fissures, broad nasal bridge, beaked nose and micrognathia. In addition, patients with RSTS have an increased, although not well documented, risk of tumor formation. |
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| Top: Ideogram of chromosome 16 and chromosomal localisation of the CREBBP gene. Middle: the genomic region including CREBBP (red) and flanking genes is zoomed. Deletions spanning CREBBP and adjacent sequences (accounting for about 10% of CREBBP mutations) are indicated by black lines. Mosaic deletions (only 3 so far detected) are asterisked; dotted lines target low-resolution mapped breakpoints. So far 22 deletions have been reported and the differently sized ones (21) are here diagrammed.
Bottom: structure of CREBBP gene and protein. Different colours are used to link gene exons (pictured by rectangles) and corresponding protein domains. Different reported point mutations (n.108 in Leiden Open Variation Database) are shown: filled circles (nonsense) and dotted circles (frameshift), squares (missense) and triangles (splicing). Most mutations cluster to exons encoding the HAT domain.
Known domains from the carbossi-terminal are: Q= poly Glutaminic stretch, Zn=zinc-finger, HAT= acetyl transferasic, Bromo= Bromodomain, KIX= CREB binding). |
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| | |
| The translocation t(8;16)(p11;p13) of acute myeloid leukaemia fuses a putative acetyltransferase to the CREB-binding protein. |
| Borrow J, Stanton VP Jr, Andresen JM, Becher R, Behm FG, Chaganti RS, Civin CI, Disteche C, Dube I, Frischauf AM, Horsman D, Mitelman F, Volinia S, Watmore AE, Housman DE. |
| Nat Genet. 1996 Sep;14(1):33-41. |
| PMID 8782817 |
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| p300 and CBP as transcriptional regulators and targets of oncogenic events. |
| Eckner R. |
| Biol Chem. 1996 Nov;377(11):685-8. (REVIEW) |
| PMID 8960368 |
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| Construction of a 1.2-Mb contig surrounding, and molecular analysis of, the human CREB-binding protein (CBP/CREBBP) gene on chromosome 16p13.3. |
| Giles RH, Petrij F, Dauwerse HG, den Hollander AI, Lushnikova T, van Ommen GJ, Goodman RH, Deaven LL, Doggett NA, Peters DJ, Breuning MH. |
| Genomics. 1997 May 15;42(1):96-114. |
| PMID 9177780 |
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| The multifunctional role of the co-activator CBP in transcriptional regulation. |
| Goldman PS, Tran VK, Goodman RH. |
| Recent Prog Horm Res. 1997;52:103-19; discussion 119-20. (REVIEW) |
| PMID 9238849 |
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| MLL is fused to CBP, a histone acetyltransferase, in therapy-related acute myeloid leukemia with a t(11;16)(q23;p13.3). |
| Sobulo OM, Borrow J, Tomek R, Reshmi S, Harden A, Schlegelberger B, Housman D, Doggett NA, Rowley JD, Zeleznik-Le NJ. |
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| PMID 9238046 |
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| The t(11;16)(q23;p13) translocation in myelodysplastic syndrome fuses the MLL gene to the CBP gene. |
| Taki T, Sako M, Tsuchida M, Hayashi Y. |
| Blood. 1997 Jun 1;89(11):3945-50. |
| PMID 9166831 |
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| p300 and CBP: partners for life and death. |
| Giordano A, Avantaggiati ML. |
| J Cell Physiol. 1999 Nov;181(2):218-30. (REVIEW) |
| PMID 10497301 |
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| Developmentally regulated expression of the transcriptional cofactors/histone acetyltransferases CBP and p300 during mouse embryogenesis. |
| Partanen A, Motoyama J, Hui CC. |
| Int J Dev Biol. 1999 Sep;43(6):487-94. |
| PMID 10610021 |
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| Function for p300 and not CBP in the apoptotic response to DNA damage. |
| Yuan ZM, Huang Y, Ishiko T, Nakada S, Utsugisawa T, Shioya H, Utsugisawa Y, Shi Y, Weichselbaum R, Kufe D. |
| Oncogene. 1999 Oct 7;18(41):5714-7. |
| PMID 10523850 |
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| CBP/p300 histone acetyl-transferase activity is important for the G1/S transition. |
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| Oncogene. 2000 May 11;19(20):2430-7. |
| PMID 10828885 |
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| p300/CBP/p53 interaction and regulation of the p53 response. |
| Grossman SR. |
| Eur J Biochem. 2001 May;268(10):2773-8. (REVIEW) |
| PMID 11358491 |
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| CBP, a transcriptional coactivator and acetyltransferase. |
| McManus KJ, Hendzel MJ. |
| Biochem Cell Biol. 2001;79(3):253-66. (REVIEW) |
| PMID 11467739 |
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| CREB-binding protein and p300 in transcriptional regulation. |
| Vo N, Goodman RH. |
| J Biol Chem. 2001 Apr 27;276(17):13505-8. Epub 2001 Mar 8. (REVIEW) |
| PMID 11279224 |
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| CBP and p300: versatile coregulators with important roles in hematopoietic gene expression. |
| Blobel GA. |
| J Leukoc Biol. 2002 Apr;71(4):545-56. (REVIEW) |
| PMID 11927640 |
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| The versatile functions of the transcriptional coactivators p300 and CBP and their roles in disease. |
| Janknecht R. |
| Histol Histopathol. 2002 Apr;17(2):657-68. (REVIEW) |
| PMID 11962765 |
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| Transcriptional control of the inflammatory response: a role for the CREB-binding protein (CBP). |
| Matt T. |
| Acta Med Austriaca. 2002;29(3):77-9. (REVIEW) |
| PMID 12168567 |
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| Ca(2+)/CREB/CBP-dependent gene regulation: a shared mechanism critical in long-term synaptic plasticity and neuronal survival. |
| Bito H, Takemoto-Kimura S. |
| Cell Calcium. 2003 Oct-Nov;34(4-5):425-30. (REVIEW) |
| PMID 12909086 |
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| The multifunctional role of E1A in the transcriptional regulation of CREB/CBP-dependent target genes. |
| Brockmann D, Esche H. |
| Curr Top Microbiol Immunol. 2003;272:97-129. (REVIEW) |
| PMID 12747548 |
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| Chromatin acetylation, memory, and LTP are impaired in CBP+/- mice: a model for the cognitive deficit in Rubinstein-Taybi syndrome and its amelioration. |
| Alarcon JM, Malleret G, Touzani K, Vronskaya S, Ishii S, Kandel ER, Barco A. |
| Neuron. 2004 Jun 24;42(6):947-59. |
| PMID 15207239 |
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| CBP and p300: HATs for different occasions. |
| Kalkhoven E. |
| Biochem Pharmacol. 2004 Sep 15;68(6):1145-55. (REVIEW) |
| PMID 15313412 |
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| Targeting CREB-binding protein (CBP) loss of function as a therapeutic strategy in neurological disorders. |
| Rouaux C, Loeffler JP, Boutillier AL. |
| Biochem Pharmacol. 2004 Sep 15;68(6):1157-64. (REVIEW) |
| PMID 15313413 |
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| Rubinstein-Taybi syndrome. |
| Hennekam RC. |
| Eur J Hum Genet. 2006 Sep;14(9):981-5. Epub 2006 Jul 26. (REVIEW) |
| PMID 16868563 |
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| High frequency of mosaic CREBBP deletions in Rubinstein-Taybi syndrome patients and mapping of somatic and germ-line breakpoints. |
| Gervasini C, Castronovo P, Bentivegna A, Mottadelli F, Faravelli F, Giovannucci-Uzielli ML, Pessagno A, Lucci-Cordisco E, Pinto AM, Salviati L, Selicorni A, Tenconi R, Neri G, Larizza L. |
| Genomics. 2007 Nov;90(5):567-73. Epub 2007 Sep 12. |
| PMID 17855048 |
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| CBP/p300 are bimodal regulators of Wnt signaling. |
| Li J, Sutter C, Parker DS, Blauwkamp T, Fang M, Cadigan KM. |
| EMBO J. 2007 May 2;26(9):2284-94. Epub 2007 Apr 5. |
| PMID 17410209 |
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| Aberrant forms of histone acetyltransferases in human disease. |
| Van Beekum O, Kalkhoven E. |
| Subcell Biochem. 2007;41:233-62. (REVIEW) |
| PMID 17484131 |
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| The structural basis of protein acetylation by the p300/CBP transcriptional coactivator. |
| Liu X, Wang L, Zhao K, Thompson PR, Hwang Y, Marmorstein R, Cole PA. |
| Nature. 2008 Feb 14;451(7180):846-50. |
| PMID 18273021 |
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| t(8;16)(p11;p13) predisposes to a transient but potentially recurring neonatal leukemia. |
| Wong KF, Yuen HL, Siu LL, Pang A, Kwong YL. |
| Hum Pathol. 2008 Jul 25. [Epub ahead of print] |
| PMID 18657848 |
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