PIAS1 and PIAS3 Protein Interaction with HsRad51 and HeRad52 May Downregulate Recombination Repair in Human Mammary Epithelial Cells

摘要

Characterization of BRCA1 and BRCA2 has strongly implicated homologous recombinational repair (HRR) as a pathway important in breast cancer. Rad51 and Rad52 are two additional proteins important for HRR, and we are characterizing some proteins that interact with them. Using the yeast two-hybrid system, we had shown that the human proteins PIAS1 and PIAS3 (protein inhibitors of activated STATs) specifically interact with Rad51 and Rad52. Recently, PIAS1 has been shown by others to interact with p53 and to be involved in its sumoylation. Sumoylation is related to ubiquitination, but does not appear to tag a protein for degradation. During the last year we confirmed the interaction between PIAS1 and hRad51 using purified hRad51 and PIAS1-GST fusion proteins. In addition, the regions of PIAS1 that interact with Rad51, Rad52 and P53 were mapped and shown to completely overlap. This region is the acidic domain of PIAS1 (PIAS1-AD).