p300/CBP and cancer.
p300 and cyclic AMP response element-binding protein (CBP) are adenoviral E1A-binding proteins involved in multiple cellular processes, and function as transcriptional co-factors and histone acetyltransferases. Germline mutation of CBP results in Rubinstein-Taybi syndrome, which is characterized by an increased predisposition to childhood malignancies. Furthermore, somatic mutations of p300 and CBP occur in a number of malignancies. Chromosome translocations target CBP and, less commonly, p300 in acute myeloid leukemia and treatment-related hematological disorders. p300 mutations in solid tumors result in truncated p300 protein products or amino-acid substitutions in critical protein domains, and these are often associated with inactivation of the second allele. A mouse model confirms that p300 and CBP function as suppressors of hematological tumor formation. The involvement of these proteins in critical tumorigenic pathways (including TGF-beta, p53 and Rb) provides a mechanistic route as to how their inactivation could result in cancer.
Iyer
Narayanan Gopalakrishna
NG
Cancer Genomics Program, Department of Oncology, University of Cambridge, Hutchison/MRC Research Centre, Cambridge CB2 2XZ, UK.
Ozdag
Hilal
H
Caldas
Carlos
C
D000123:Acetyltransferases / Q000235:genetics / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D016147:Genes, Tumor Suppressor / Q000502:physiology; D051548:Histone Acetyltransferases; D006801:Humans; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D012415:Rubinstein-Taybi Syndrome / Q000235:genetics / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor
D000123:Acetyltransferases; D018797:Cell Cycle Proteins; D051548:Histone Acetyltransferases; D009687:Nuclear Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor