Transcriptome-wide identification and competitive disruption of sacum-binding partners in human colorectal cancer.

Human sacum is regulatory adaptor protein involved in cellular signaling network of colorectal cancer. Molecular evidence suggests that the protein is integrated into oncogenic signaling network by binding to SH3-containing proteins through its proline-rich motifs. In this study, we have performed a transcriptome-wide analysis and identification of sacum-binding partners in the genome profile of human colorectal cancer. The sacum-binding potency of SH3-containing proteins found in colorectal cancer was investigated by using bioinformatics modeling and intermolecular binding analysis. With the protocol we were able to predict those high-affinity domain binders of the proline-rich peptides of human sacum in a high-throughput manner, and to analyze sequence-specific interaction in the domain-peptide recognition at molecular level. Consequently, a number of putative domain binders with both high affinity and specificity were identified, from which the Src SH3 domain was selected as a case study and tested for its binding activity towards the sacum peptides. We also designed two peptide variants that may have potent capability to competitively disrupt sacum interaction with its partners.