Refining the pH response inAspergillus nidulans: a modulatory triad involving PacX, a novel zinc binuclear cluster protein

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TheAspergillus nidulansPacC transcription factor mediates gene regulation in response to alkaline ambient pH which, signalled by the Pal pathway, results in the processing of PacC72 to PacC27 via PacC53. Here we investigate two levels at which the pH regulatory system is transcriptionally moderated by pH and identify and characterise a new component of the pH regulatory machinery, PacX. Transcript level analysis and overexpression studies demonstrate that repression of acid-expressedpalF, specifying the Pal pathway arrestin, probably by PacC27 and/or PacC53, prevents an escalating alkaline pH response. Transcript analyses using a reporter and constitutively expressedpacCtrans-alleles show thatpacCpreferential alkaline-expression results from derepression by depletion of the acid-prevalent PacC72 form. We additionally show thatpacCrepression requires PacX.pacXmutations suppress PacC processing recalcitrant mutations, in part, through derepressed PacC levels resulting in traces of PacC27 formed by pH-independent proteolysis.pacXwas cloned byimpalatransposon mutagenesis. PacX, with homologues within the Leotiomyceta, has an unusual structure with an amino-terminal coiled-coil and a carboxy-terminal zinc binuclear cluster.pacXmutations indicate the importance of these regions. One mutation, an unprecedented finding inA. nidulansgenetics, resulted from an insertion of an endogenousFot1-like transposon.

The Aspergillus nidulans pH response, mediated by PacC which is proteolytically activated in response to Pal mediated alkaline pH signalling, moderates itself. pacC is negatively autoregulated by the acid prevalent form PacC72 and a runaway pH response is prevented by negative feedback at signalling gene palF. PacX, a zinc binuclear cluster protein with unusual architecture and restricted taxonomic distribution, tempers PacC activity and is required to tether the pH response to the ambient pH signal.

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