Peroxide sensors for the fission yeast stress-activated mitogen-activated protein kinase pathway

Citation
V. Buck et al., Peroxide sensors for the fission yeast stress-activated mitogen-activated protein kinase pathway, MOL BIOL CE, 12(2), 2001, pp. 407-419
Citations number
74
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Cell & Developmental Biology
Journal title
MOLECULAR BIOLOGY OF THE CELL
ISSN journal
1059-1524 → ACNP
Volume
12
Issue
2
Year of publication
2001
Pages
407 - 419
Database
ISI
SICI code
1059-1524(200102)12:2<407:PSFTFY>2.0.ZU;2-R
Abstract
The Schizosaccharomyces pombe stress-activated Sty1p/Spc1p mitogen-activate d protein (MAP) kinase regulates gene expression through the Atf1p and Pap1 p transcription factors, homologs of human ATF2 and c-jun, respectively. Mc s4p, a response regulator protein, acts upstream of Sty1p by binding the Wa k1p/Wis4p MAP kinase kinase kinase. We show that phosphorylation. of Mcs4p on a conserved aspartic acid residue is required for activation of Sty1p on ly in response to peroxide stress. Mcs4p acts in a conserved phospho-relay system initiated by two PAS/PAC domain-containing histidine kinases, Mak2p and Mak3p. In the absence of Mak2p or Mak3p, Sty1p fails to phosphorylate t he Atf1p transcription factor or induce Atf1p-dependent gene expression. As a consequence, cells lacking Mak2p and Mak3p are sensitive to peroxide att ack in the absence of Prr1p, a distinct response regulator protein that fun ctions in association with Pap1p. The Mak1p histidine kinase, which also co ntains PAS/PAC repeats, does not regulate Sty1p or Atf1p but is partially r equired for Pap1p- and Prr1p-dependent transcription. We conclude that the transcriptional response to free radical attack is initiated by at least tw o distinct phospho-relay pathways in fission yeast.