Programmed cell death (PCD), with similarities to animal apoptosis, was induced in tomato suspension cells by the topoisomerase I inhibitor camptothecin. Previously, a differential display screening was performed to isolate genes differentially expressed during camptothecin-induced cell death. As a result, the new tomato gene Le-pirin was isolated, whose mRNA levels dramatically increase during camptothecin-induced PCD. Le-pirin mRNA accumulation is also observed when cell death is triggered by the mycotoxin fumonisin-B1, but not when the suspension cells are treated with stress-related compounds such as ethylene, methyl jasmonate or salicylic acid. The caspase inhibitor Z-Asp-CH2-DCB and the calcium channel blocker LaCl3 effectively delayed whereas ethylene greatly stimulated camptothecin-induced PCD and the accumulation of Le-pirin mRNA. The Le-pirin encoded protein shows 56% identity with the human protein PIRIN, a nuclear factor reported to interact with the human oncogene Bcl-3. Human PIRIN stabilizes the formation of quaternary complexes between Bcl-3, the anti-apoptotic transcription factor NF-kappaB and its DNA target sequences in vitro. The isolation of Le-pirin and its implication in plant PCD provides new clues on the role of putative NF-kappaB-associated pathways in plant defence mechanisms.