Functional Analysis of the Transcriptional Co-activator CBP in Wnt-signaling Dependent Mammary Carcinogenesis
Abstract
Wnt signaling is mediated by a multi-component cascade that relays the signal from cell membrane to nuclear TCF-beta-catenin transcriptional complex. Genetic study has implicated CREB-Binding Protein (CBP) as a negative regulator of Wnt signaling, suggesting that CBP could modulate the wnt-induced carcinogenesis. In contrast to our original hypothesis that CBP-mediated acetylation negatively regulates TCF-dependent transcription, we have previously found that CBP potentiates TCF-beta-catenin transcriptional activity by physically interacting with beta-catenin. We then hypothesize that in the absence of beta-catenin, CBP facilitates the function of TCF as a transcriptional repressor in the context of chromatin. Upon binding to beta-catenin, CBP is converted to a classical transcriptional co-activator that activates wnt-dependent downstream target genes. To investigate this possibility, we have created analyzed chromatinized reporters based on chromosomal reporter or by replication-competent reporter plasmid. Preliminary study on these reporters indicate that TCF binding sites confer transcriptional repression activity. We are now investigating whether CBP and TCF members modulates this repression activity. On the TCF4 acetylation front, by analyzing TCF acetylation pattern, we obtained evidence that there are more than one acetylation sites present in TCF4. We are currently mapping the novel acetylation sites and analyze their potential functions.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2002
- Accession Number
- ADA404621
Entities
People
- Tso-pang Yao
Organizations
- Duke University Hospital