Scientists Validate Method to Measure Protein Interactions

Researchers working with the p73 homologue of the tumor-suppressor gene p73 have described the mechanism by which the Wwox tumor suppressor protein interacts with p73, an interaction that increases apoptosis and decreases the likelihood of tumor development.

The p73 gene shares many structural and functional features of p53, including a 63% homology with a remarkable conservation of critical residues that are known to be important for the binding of p53 to target genes or proper folding of p53. The C-terminal domain of p53 and p73 are quite distinct, however. The p73 gene has been mapped to human chromosome 1p36, a region that is frequently deleted in a variety of human cancers including neuroblastoma, colon cancer, and breast cancer.

Scientists at Thomas Jefferson University (Philadelphia, PA, USA) and researchers at Cytogen Corp. (Princeton, NJ, USA) reported in the March 30, 2004, issue of the Proceedings of the [U.S.] National Academy of Sciences that Wwox physically interacted via its first WW domain with the p53 homologue, p73. The tyrosine kinase, Src, phosphorylated Wwox at tyrosine 33 in the first WW domain and enhanced its binding to p73. Wwox expression triggered redistribution of nuclear p73 to the cytoplasm and, hence, suppressed its transcriptional activity. In addition, cytoplasmic p73 contributed to the activity of Wwox leading to apoptosis. These findings were obtained using Cytogen's in vitro signal transduction pathway discovery platform.

"In the present study, we have demonstrated the physical interaction between the recently discovered Wwox and the p53 homologue, p73,” explained senior author Dr.Carlo Croce, professor of microbiology and immunology at Thomas Jefferson University. "Since the Wwox protein contains two WW domains that are generally known to mediate protein-protein interaction, Cytogen's robust WW domain interaction data allowed us to efficiently reveal a functional cross-talk between p73 and the Wwox tumor suppressor protein. The study results help establish that the company's high-throughput method to measure protein interactions compares favorably with other more complex techniques and further validates this method of elucidating and identifying protein interactions.”





Related Links:
Thomas Jefferson University
Cytogen Corp.