©2007 by MEDIMOND S.r.l. 45H618R9063 CP motifs, Hap1 and Heme Signaling

Heme is known to regulate the activity of diverse proteins in organisms ranging from bacterium to human. Heme dynamically and reversibly regu-lates the activity of signal transducers and transcriptional regulators by bind-ing to CP motifs. In yeast, heme serves as an oxygen messenger and mediates oxygen regulation of various genes. Our genomic and computational analyses suggest that heme is a major factor in oxygen regulation of gene expression. The yeast heme activator protein Hap1 is an important regulator mediating heme regulation. Our results show that heme activation of Hap1 transcrip-tional activity requires one CP motif (HRM7) of Hap1 and the molecular chaperone Hsp90. Interestingly, we found that the mammalian Raf proteins contain a CP motif and are regulated by heme