Insight into the tumor suppressor function of CBP through the viral oncoprotein tax.
CREB binding protein (CBP) is a cellular coactivator protein that regulates essentially all known pathways of gene expression. The transcriptional coactivator properties of CBP are utilized by at least 25 different transcription factors representing nearly all known classes of DNA binding proteins. Once bound to their target genes, these transcription factors are believed to tether CBP to the promoter, leading to activated transcription. CBP functions to stimulate transcription through direct recruitment of the general transcription machinery as well as acetylation of both histone and transcription factor substrates. Recent observations indicate that a critical dosage of CBP is required for normal development and tumor suppression, and that perturbations in CBP concentrations may disrupt cellular homeostasis. Furthermore, there is accumulating evidence that CBP deregulation plays a direct role in hematopoietic malignancies. However, the molecular events linking CBP deregulation and malignant transformation are unclear. Further insight into the function of CBP, and its role as a tumor suppressor, can be gained through recent studies of the human T-cell leukemia virus, type I (HTLV-I) Tax oncoprotein. Tax is known to utilize CBP to stimulate transcription from the viral promoter. However, recent data suggest that as a consequence of the Tax-CBP interaction, many cellular transcription factor pathways may be deregulated. Tax disruption of CBP function may play a key role in transformation of the HTLV-I-infected cell. Thus, Tax derailment of CBP may lend important information about the tumor suppressor properties of CBP and serve as a model for the role of CBP in hematopoietic malignancies.
Van Orden
K
K
Department of Biochemistry and Molecular Biology, Colorado State University, Fort Collins 80523-1870, USA.
Nyborg
J K
JK
D000818:Animals; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D016356:Gene Products, tax / Q000378:metabolism*; D016147:Genes, Tumor Suppressor; D019337:Hematologic Neoplasms / Q000235:genetics* / Q000821:virology; D015368:Human T-lymphotropic virus 1 / Q000235:genetics*; D006801:Humans; D011401:Promoter Regions, Genetic; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic
D017362:Cyclic AMP Response Element-Binding Protein; D016356:Gene Products, tax; D014157:Transcription Factors