Coordinated regulation of calcium homeostasis and pathogenicity by a dual-action transcriptional regulator Cas5 [RNA-Seq]

Although studies have shown that the transcription factor Crz1 is the master regulator of calcium (Ca2+) homeostasis, accumulating evidence supports a clear involvement of other participants in this biological process.

Here, following a high-throughput genetic screen, we identified the transcription factor Cas5 as a novel positive regulator of Ca2+ homeostasis in C. albicans. Mechanistically, Cas5 modulates Crz1 dephosphorylation, nuclear localization and Crz1-dependent signaling pathway by inhibiting protein kinase Tpk1 to maintain Ca2+ homeostasis. Furthermore, our study confirms that the calcineurin-mediated virulence is dependent on transcription factor Cas5 in a Crz1-independent manner, complementing a long-standing knowledge gap in the regulation of virulence by calcineurin.