Core regulatory components of the PHO pathway are conserved in the methylotrophic yeast Hansenula polymorpha
In Saccharomyces cerevisiae, phosphate acquisition enzymes are regulated by a cyclin-dependent kinase (Pho85), a cyclin (Pho80), the cyclin-dependent kinase inhibitor Pho81, and the helix-loop-helix transcription factor Pho4 (the PHO system). Previous studies in Aspergillus nidulans indicate that a Pho85-like kinase, PHOA, does not regulate the classic PHO system but regulates development in a phosphate-dependent manner. A Pho80-like cyclin has now been isolated through its interaction with PHOA. Surprisingly, unlike PHOA, An-PHO80 does play a negative role in the PHO system. Similarly, an ortholog of Pho4 previously identified genetically as palcA also regulates the PHO system. However, An-PHO81, a putative cyclin-dependent kinase inhibitor, does not regulate the PHO system. Therefore, there are significant differences between the classic PHO system conserved between S. cerevisiae and Neurospora crassa compared with that which has evolved in A. nidulans. Most interestingly, under low phosphate conditions, the An-PHO80 cyclin also promotes sexual development while having a negative effect on asexual development. These effects are independent of the role An-PHO80 has in the classic PHO system. However, in high phosphate medium, An-PHO80 affects development because of deregulation of the PHO system as loss of palcA(Pho4) function negates the developmental defects caused by lack of An-pho80. Therefore, under low phosphate conditions the An-PHO80 cyclin regulates development independently of the PHO system, whereas in high phosphate it affects development through the PHO system. The data indicate that a single cyclin can control various aspects of growth and development in a multicellular organism.