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Deciphering the role of the signal- and Sty1 kinase-dependent phosphorylation of the stress-responsive transcription factor Atf1 on gene activation.
J Biol Chem. 2017 08 18; 292(33):13635-13644.JB

Abstract

Adaptation to stress triggers the most dramatic shift in gene expression in fission yeast (Schizosaccharomyces pombe), and this response is driven by signaling via the MAPK Sty1. Upon activation, Sty1 accumulates in the nucleus and stimulates expression of hundreds of genes via the nuclear transcription factor Atf1, including expression of atf1 itself. However, the role of stress-induced, Sty1-mediated Atf1 phosphorylation in transcriptional activation is unclear. To this end, we expressed Atf1 phosphorylation mutants from a constitutive promoter to uncouple Atf1 activity from endogenous, stress-activated Atf1 expression. We found that cells expressing a nonphosphorylatable Atf1 variant are sensitive to oxidative stress because of impaired transcription of a subset of stress genes whose expression is also controlled by another transcription factor, Pap1. Furthermore, cells expressing a phospho-mimicking Atf1 mutant display enhanced stress resistance, and although expression of the Pap1-dependent genes still relied on stress induction, another subset of stress-responsive genes was constitutively expressed in these cells. We also observed that, in cells expressing the phospho-mimicking Atf1 mutant, the presence of Sty1 was completely dispensable, with all stress defects of Sty1-deficient cells being suppressed by expression of the Atf1 mutant. We further demonstrated that Sty1-mediated Atf1 phosphorylation does not stimulate binding of Atf1 to DNA but, rather, establishes a platform of interactions with the basal transcriptional machinery to facilitate transcription initiation. In summary, our results provide evidence that Atf1 phosphorylation by the MAPK Sty1 is required for oxidative stress responses in fission yeast cells by promoting transcription initiation.

Authors+Show Affiliations

From the Oxidative Stress and Cell Cycle Group and.From the Oxidative Stress and Cell Cycle Group and.From the Oxidative Stress and Cell Cycle Group and.From the Oxidative Stress and Cell Cycle Group and.From the Oxidative Stress and Cell Cycle Group and.Structural Bioinformatics Laboratory (GRIB), Universitat Pompeu Fabra, C/ Dr. Aiguader 88, 08003 Barcelona, Spain.From the Oxidative Stress and Cell Cycle Group and elena.hidalgo@upf.edu.

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

28652406

Citation

Salat-Canela, Clàudia, et al. "Deciphering the Role of the Signal- and Sty1 Kinase-dependent Phosphorylation of the Stress-responsive Transcription Factor Atf1 On Gene Activation." The Journal of Biological Chemistry, vol. 292, no. 33, 2017, pp. 13635-13644.
Salat-Canela C, Paulo E, Sánchez-Mir L, et al. Deciphering the role of the signal- and Sty1 kinase-dependent phosphorylation of the stress-responsive transcription factor Atf1 on gene activation. J Biol Chem. 2017;292(33):13635-13644.
Salat-Canela, C., Paulo, E., Sánchez-Mir, L., Carmona, M., Ayté, J., Oliva, B., & Hidalgo, E. (2017). Deciphering the role of the signal- and Sty1 kinase-dependent phosphorylation of the stress-responsive transcription factor Atf1 on gene activation. The Journal of Biological Chemistry, 292(33), 13635-13644. https://doi.org/10.1074/jbc.M117.794339
Salat-Canela C, et al. Deciphering the Role of the Signal- and Sty1 Kinase-dependent Phosphorylation of the Stress-responsive Transcription Factor Atf1 On Gene Activation. J Biol Chem. 2017 08 18;292(33):13635-13644. PubMed PMID: 28652406.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Deciphering the role of the signal- and Sty1 kinase-dependent phosphorylation of the stress-responsive transcription factor Atf1 on gene activation. AU - Salat-Canela,Clàudia, AU - Paulo,Esther, AU - Sánchez-Mir,Laura, AU - Carmona,Mercè, AU - Ayté,José, AU - Oliva,Baldo, AU - Hidalgo,Elena, Y1 - 2017/06/26/ PY - 2017/05/02/received PY - 2017/06/23/revised PY - 2017/6/28/pubmed PY - 2017/9/7/medline PY - 2017/6/28/entrez KW - Atf1 KW - Schizosaccharomyces pombe KW - Sty1 KW - mitogen-activated protein kinase (MAPK) KW - oxidative stress KW - phosphorylation KW - transcription regulation SP - 13635 EP - 13644 JF - The Journal of biological chemistry JO - J Biol Chem VL - 292 IS - 33 N2 - Adaptation to stress triggers the most dramatic shift in gene expression in fission yeast (Schizosaccharomyces pombe), and this response is driven by signaling via the MAPK Sty1. Upon activation, Sty1 accumulates in the nucleus and stimulates expression of hundreds of genes via the nuclear transcription factor Atf1, including expression of atf1 itself. However, the role of stress-induced, Sty1-mediated Atf1 phosphorylation in transcriptional activation is unclear. To this end, we expressed Atf1 phosphorylation mutants from a constitutive promoter to uncouple Atf1 activity from endogenous, stress-activated Atf1 expression. We found that cells expressing a nonphosphorylatable Atf1 variant are sensitive to oxidative stress because of impaired transcription of a subset of stress genes whose expression is also controlled by another transcription factor, Pap1. Furthermore, cells expressing a phospho-mimicking Atf1 mutant display enhanced stress resistance, and although expression of the Pap1-dependent genes still relied on stress induction, another subset of stress-responsive genes was constitutively expressed in these cells. We also observed that, in cells expressing the phospho-mimicking Atf1 mutant, the presence of Sty1 was completely dispensable, with all stress defects of Sty1-deficient cells being suppressed by expression of the Atf1 mutant. We further demonstrated that Sty1-mediated Atf1 phosphorylation does not stimulate binding of Atf1 to DNA but, rather, establishes a platform of interactions with the basal transcriptional machinery to facilitate transcription initiation. In summary, our results provide evidence that Atf1 phosphorylation by the MAPK Sty1 is required for oxidative stress responses in fission yeast cells by promoting transcription initiation. SN - 1083-351X UR - https://www.unboundmedicine.com/medline/citation/28652406/Deciphering_the_role_of_the_signal__and_Sty1_kinase_dependent_phosphorylation_of_the_stress_responsive_transcription_factor_Atf1_on_gene_activation_ L2 - https://linkinghub.elsevier.com/retrieve/pii/M117.794339 DB - PRIME DP - Unbound Medicine ER -