Compositions and methods for modulating BRD4 bioactivity

摘要

Compositions and methods for increasing or decreasing DNA repair are provided. Composition includes a Brd4 polypeptide, fragment, fusion, or variant thereof. The fusion protein can include a protein transduction, a targeting domain, or a combination thereof to enhance delivery of the fusion protein to the interior of a particular target cell, such as a cancer cell. Inhibitory nucleic acids that target a Brd4 mRNA and antibodies that target a Brd4 polypeptide are also disclosed. The inhibitory nucleic acid or antibody can target a sequence or epitope on Brd4 isoform B that is absent on Brd4 isoform A and Brd4 isoform C. Methods for increasing or decreasing the sensitivity of cells to a DNA damaging agent, methods of treating cancer, and methods of determining cells' sensitivity to a DNA damaging agent are also disclosed.

主权项

1. A method of reducing the DNA damage response in a cell comprising contacting the cell with an effective amount of a Brd4 polypeptide or a nucleic acid encoding the Brd4 polypeptide to reduce the DNA damage response in the cell,
wherein the Brd4 polypeptide comprises at least 95% sequence identity to the Brd4 isoform B having the amino acid sequence of SEQ ID NO:22.