Figure 6
The evolution of the roles of CBC and its regulatory subunits in the control of fungal iron homeostasis. In Schizosaccharomyces pombe, Php4 plays an important role in the iron starvation response by repressing the iron consuming genes through its interaction with the CCAAT Binding Complex (CBC) which is mediated by its Hap4Like domain (Hap4L) (reviewed in ref. 15). In C. glabrata, Yap5 is a major regulator of the iron stress response which activates iron consuming genes21, 29. Yap5 binding to its targets requires CBC, probably by direct interaction with Hap5 through its vestigial Hap4L domain (this work). However, Yap5 also interacts directly with DNA through its bZIP domain and this interaction is essential for its regulatory activity29, 35, 36. Interestingly enough, the situation in filamentous ascomycetes (e.g. Aspergillus or Fusarium species) and in C. albicans is an intermediate between S. pombe and S. cerevisiae. HapX plays an important dual role in activating the iron stress response and in repressing the same genes in iron starvation11, 12, 18, 20. HapX interacts with CBC through its conserved Hap4L domain, but it also directly contributes to the binding of the CBC-HapX complex to a bipartite DNA motif, probably through its bZIP sequence18, 20, 24, 25.
