1. p300/CBP and cancer
- Author
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Narayanan Gopalakrishna Iyer, Carlos Caldas, and Hilal Özdağ
- Subjects
Cancer Research ,Protein domain ,Cell Cycle Proteins ,P300-CBP Transcription Factors ,Biology ,medicine.disease_cause ,Germline mutation ,Acetyltransferases ,Neoplasms ,Genetics ,medicine ,Humans ,Genes, Tumor Suppressor ,p300-CBP Transcription Factors ,Molecular Biology ,Transcription factor ,Histone Acetyltransferases ,Rubinstein-Taybi Syndrome ,Mutation ,Nuclear Proteins ,Myeloid leukemia ,Cancer ,medicine.disease ,Molecular biology ,Trans-Activators ,Carcinogenesis ,Transcription Factors - Abstract
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.
- Published
- 2004