Atf1 is a target of the mitogen-activated protein kinase Pmk1 and regulates cell integrity in fission yeast.
In fission yeast, knockout of the calcineurin gene resulted in hypersensitivity to Cl(-), and the overexpression of pmp1(+) encoding a dual-specificity phosphatase for Pmk1 mitogen-activated protein kinase (MAPK) or the knockout of the components of the Pmk1 pathway complemented the Cl(-) hypersensitivity of calcineurin deletion. Here, we showed that the overexpression of ptc1(+) and ptc3(+), both encoding type 2C protein phosphatase (PP2C), previously known to inactivate the Wis1-Spc1-Atf1 stress-activated MAPK signaling pathway, suppressed the Cl(-) hypersensitivity of calcineurin deletion. We also demonstrated that the mRNA levels of these two PP2Cs and pyp2(+), another negative regulator of Spc1, are dependent on Pmk1. Notably, the deletion of Atf1, but not that of Spc1, displayed hypersensitivity to the cell wall-damaging agents and also suppressed the Cl(-) hypersensitivity of calcineurin deletion, both of which are characteristic phenotypes shared by the mutation of the components of the Pmk1 MAPK pathway. Moreover, micafungin treatment induced Pmk1 hyperactivation that resulted in Atf1 hyperphosphorylation. Together, our results suggest that PP2C is involved in a negative feedback loop of the Pmk1 signaling, and results also demonstrate that Atf1 is a key component of the cell integrity signaling downstream of Pmk1 MAPK.
Takada
Hirofumi
H
Laboratory of Molecular Pharmacogenomics, School of Pharmaceutical Sciences, Kinki University, Higashi-Osaka, 577-8502, Japan.
Nishimura
Masayuki
M
Asayama
Yuta
Y
Mannse
Yoshiaki
Y
Ishiwata
Shunji
S
Kita
Ayako
A
Doi
Akira
A
Nishida
Aiko
A
Kai
Naoyuki
N
Moriuchi
Sayako
S
Tohda
Hideki
H
Giga-Hama
Yuko
Y
Kuno
Takayoshi
T
Sugiura
Reiko
R
D051697:Activating Transcription Factor 1 / Q000235:genetics / Q000378:metabolism*; D019703:Calcineurin / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D002473:Cell Wall / Q000201:enzymology / Q000502:physiology*; D018628:Gene Dosage / Q000235:genetics; D015966:Gene Expression Regulation, Fungal; D020935:MAP Kinase Signaling System; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D010749:Phosphoprotein Phosphatases / Q000235:genetics / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D000071636:Protein Phosphatase 2C; D012333:RNA, Messenger / Q000235:genetics; D012568:Schizosaccharomyces / Q000166:cytology* / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
D051697:Activating Transcription Factor 1; D010750:Phosphoproteins; D012333:RNA, Messenger; D029702:Schizosaccharomyces pombe Proteins; C106740:atf1 protein, S pombe; D020928:Mitogen-Activated Protein Kinases; C516338:Pmk1 protein, S pombe; D019703:Calcineurin; D010749:Phosphoprotein Phosphatases; D000071636:Protein Phosphatase 2C