Modulation of the Proliferation and Metastasis of Human Breast Tumor Cells by SLUG (IDEA)
Abstract
The objective of the project for the reporting period was to identify high affinity SLUG-regulated gene promoters from human breast cells. We over expressed 3xFLAG-tagged (C-terminal) human SLUG in the SLUG-negative MDA-MB-468 and MCF-7 cells through a lentiviral construct. Employing the ChIP-DSL techniques, we have identified 154 genes in the human breast cells that are tightly binding to the transcriptional silencer protein SLUG at the E2-boxes of their promoters. The gene promoters we are following up include those of claudin 7, VDR, UBE2D3 and dynactin 5. By mutational analysis, we identified two distinct motifs in the repressor domain of the SLUG protein as essential for the repressor function of SLUG. We further characterized the structure and function of the Pmotif of SLUG repressor domain as a unique CtBP1-recruiting site. We are planning to design peptide aptamer from the P-motif region of human SLUG protein and evaluate whether that aptamer can inhibit the repressor activity in vitro and in vivo.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2008
- Accession Number
- ADA486136
Entities
People
- Gautam Chaudhuri
Organizations
- Meharry Medical College