336 THE SYSTEMIC IRON HORMONE HEPCIDIN IS INDUCED IN MACROPHAGES BY REACTIVE OXYGEN SPECIES AND DURING PHAGOCYTOSIS OF OXIDIZED ERYTHROCYTES

Abstract

intron 2 of the Mcl-1 gene. Luciferase reporter assays revealed that wild-type p53 and the TA isoforms of p63 and p73 repress the Mcl-1 gene, while the DN isoforms of the p53 family transactivate the Mcl-1 gene via a p53 responsive element in the promoter. The antagonistic regulation of the Mcl-1 gene by the TA and DN isoforms of the p53 family was further validated by qPCR and Western-blot. Furthermore, we showed by LUMIER-Assay that the TA isoforms of the p53 family directly interact with Mcl-1 on the protein level, and thereby inactivate this anti-apoptotic protein. The interaction of the p53 family and Mcl-1 so far has been incompletely characterized. Here we show that the Mcl-1 gene is a target gene of p53 and p63. Furthermore, the p53 family proteins and Mcl-1 can interact via protein-protein interaction and thus influence the mitochondria membrane potential in mitochondriamediated apoptosis signalling.