Negative feedback regulation of calcineurin-dependent Prz1 transcription factor by the CaMKK-CaMK1 axis in fission yeast.
Bottom Line: Then, active Cmk1 binds, phosphorylates and inactivates Prz1 transcription activity whilst at the same time cmk1 expression is enhanced by Prz1 in response to Ca(2+).This work reveals that Cmk1 kinase activated by the newly identified Ckk2 counteracts calcineurin function by negatively regulating Prz1 activity which in turn is involved in activating cmk1 gene transcription.These results are the first insights into Cmk1 and Ckk2 function in Schizosaccharomyces pombe.
Affiliation: Departament de Biologia Cellular, Immunologia i Neurociències, Facultat de Medicina, Universitat de Barcelona, Institute of Biomedical Research August Pi i Sunyer (IDIBAPS), Barcelona 08036, Catalunya, Spain.Show MeSH
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Mentions: In budding yeast and mammalian cells, the activity of Crz1 and NFAT transcription factors, is regulated by different signalling pathways which affect kinases (14). This prompted us to examine whether Cmk1 is involved in negative regulation of Prz1 by analysing the Ca2+-induced CDRE transcriptional activity of Prz1 in Δcmk1 cells compared to wild-type. The reporter response of Δcmk1 cells was markedly enhanced, reflecting the increase of Prz1 transcriptional activity compared with wild-type cells (Figure 4A). In contrast, overexpression of Cmk1 suppressed the Prz1 transcriptional activity (Figure 4B), indicating that Cmk1 is indeed involved in the negative regulation of Prz1.
Affiliation: Departament de Biologia Cellular, Immunologia i Neurociències, Facultat de Medicina, Universitat de Barcelona, Institute of Biomedical Research August Pi i Sunyer (IDIBAPS), Barcelona 08036, Catalunya, Spain.