Proline-rich acidic protein 1 in Life and Death
The Proline-rich acidic protein (PRAP1) was initially identified as a gene that was differentially expressed in pregnant mouse uterus. The rat and human homologues were subsequently identified and found to be expressed abundantly in the gastrointestinal tract. This thesis describes the characterization of the physiological role of human PRAP1 in the gastrointestinal tract and its possible role(s) in pathological states. The expression of PRAP1 is significantly correlated with the degree of differentiation of gastrointestinal epithelial cells. PRAP1 is secreted into the gastrointestinal lumen and binds to the surface of bacteria. It demonstrates bactericidal activity and may aid bacterial phagocytosis. In colorectal cancer (CRC), PRAP1 is a downstream target of p53 and plays a protective role against genotoxic stressors. Repression of PRAP1 significantly enhances the anti-tumor effect of chemotherapeutic drugs used in the treatment of CRC. This is partly mediated through the abrogation of S-phase arrest in a p53 dependent manner, resulting in increased DNA damage and activation of the apoptotic pathway over cell cycle arrest. PRAP also facilitates clearance of apoptotic cells, derangement of which may lead to systemic lupus erythematosus (SLE). In conclusion, PRAP1 is multifunctional protein with antimicrobial and cell fate modulation properties, which presents a novel target in the treatment of CRC and SLE.
Networked Digital Library of Theses and Dissertations