The PCNA-associated factor KIAA0101/p15PAF binds the potential tumor suppressor product p33ING1b

The KIAA0101/p15PAF/OEATC-1 protein was initially isolated in a yeast two-hybrid screen for proliferating cell nuclear antigen (PCNA) binding partners, and was shown to bind PCNA competitively with the cell cycle regulator p21WAF. PCNA is involved in DNA replication and damage repair. Using polyclonal antisera raised against a p15PAF fusion protein, we have shown that in a range of mammalian tumor and non-tumor cell lines the endogenous p15PAF protein localises to the nucleus and the mitochondria. Under normal conditions no co-localisation with PCNA could be detected, however following exposure to UV it was possible to co-immunoprecipitate p15PAF and PCNA from a number of cell lines, suggesting a UV-enhanced association of the two proteins. Overexpression of p15PAF in mammalian cells was also found to protect cells from UV-induced cell death. Based on similarities between the behaviour of p15PAF and the potential tumor suppressor product p33ING1b, we have further shown that these two proteins interact in the same complex in cell cultures. This suggests that p15PAF forms part of a larger protein complex potentially involved in the regulation of DNA repair, apoptosis and cell cycle progression.