The DenA/DEN1 Interacting Phosphatase DipA Controls Septa Positioning and Phosphorylation-Dependent Stability of Cytoplasmatic DenA/DEN1 during Fungal Development

Dena/den1 and the cop9 signalosome (csn) represent two deneddylases which remove the ubiquitin-like nedd8 from modified target proteins and are required for distinct fungal developmental programmes. the cellular dena/den1 population is divided into a nuclear and a cytoplasmatic subpopulation which is especially enriched at septa. dena/den1 stability control mechanisms are different for the two cellular subpopulations and depend on different physical interacting proteins and the c-terminal dena/den1 phosphorylation pattern. nuclear dena/den1 is destabilized during fungal development by five of the eight csn subunits which target nuclear dena/den1 for degradation. dena/den1 becomes stabilized as a phosphoprotein at s243/s245 during vegetative growth,which is necessary to support further asexual development. after the initial phase of development,the newly identified cytoplasmatic dena/den1 interacting phosphatase dipa and an additional developmental specific c-terminal phosphorylation site at serine s253 destabilize dena/den1. outside of the nucleus,dipa is co-transported with dena/den1 in the cytoplasm between septa and nuclei. deletion of dipa resulted in increased dena/den1 stability in a strain which is unresponsive to illumination. the mutant strain is dysregulated in cytokinesis and impaired in asexual development. our results suggest a dual phosphorylation-dependent dena/den1 stability control with stabilizing and destabilizing modifications and physical interaction partner proteins which function as control points in the nucleus and the cytoplasm. © 2016 schinke et al.