The AMPK, Snf1, Negatively Regulates the Hog1 MAPK Pathway in ER Stress Response

English version České info

All organisms are always exposed to several environmental stresses, including ultraviolet, heat, and chemical compounds. Therefore, every cell possesses defense mechanisms to maintain their survival under stressed conditions. Numerous studies have shown that a family of protein kinases plays a principal role in adaptive response to environmental stresses and perturbation of their regulation is implicated in a variety of human pathologies, such as cancer and neurodegenerative diseases. Elucidation of molecular mechanisms controlling their activities is still important not only for understanding how the organism acquires stress tolerance, but also for development of therapies for various diseases. In Saccharomyces cerevisiae, the Hog1 stress-responsive MAP kinase is activated by ER stress and coordinates a pleiotropic response to ER stress. However, the mechanisms for regulating Hog1 activity during ER stress response remain poorly understood. In this paper, we demonstrate that a Saccharomyces cerevisiae ortholog of mammalian AMP–activated protein kinase (AMPK), Snf1, negatively regulates Hog1 in ER stress response. ER stress induces expression of Ssk1, a specific activator of the Hog1 MAPK cascade. Snf1 lowers the expression level of Ssk1, thereby downregulating the signaling from upstream components to the Hog1 MAPK cascade. The activity of Snf1 is also enhanced by ER stress. Thus, our data suggest that Snf1 plays an important role in regulation of ER stress response signal mediated by Hog1.

Vyšlo v časopise: The AMPK, Snf1, Negatively Regulates the Hog1 MAPK Pathway in ER Stress Response. PLoS Genet 11(9): e32767. doi:10.1371/journal.pgen.1005491
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005491

Souhrn

Zdroje

1. Walter P, Ron D. The unfolded protein response: from stress pathway to homeostatic regulation. Science. 2011;334: 1081–1086. doi: 10.1126/science.1209038 22116877

2. Lindholm D, Wootz H, Korhonen L. ER stress and neurodegenerative diseases. Cell Death Differ. 2006;13: 385–392. 16397584

3. Mori K. Signalling pathways in the unfolded protein response: development from yeast to mammals. J Biochem. 2009;146: 743–750. doi: 10.1093/jb/mvp166 19861400

4. Parsons AB, Brost RL, Ding H, Li Z, Zhang C, Sheikh B, et al. Integration of chemical-genetic and genetic interaction data links bioactive compounds to cellular target pathways. Nat Biotechnol. 2004;22: 62–69. 14661025

5. Hedbacker K, Carlson M. SNF1/AMPK pathways in yeast. Front Biosci. 2008;13: 2408–2420. 17981722

6. Broach JR. Nutritional control of growth and development in yeast. Genetics. 2012;192: 73–105. doi: 10.1534/genetics.111.135731 22964838

7. Hardie DG, Ross FA, Hawley SA. AMPK: a nutrient and energy sensor that maintains energy homeostasis. Nat Rev Mol Cell Biol. 2012;13: 251–262. doi: 10.1038/nrm3311 22436748

8. Estruch F, Treitel MA, Yang X, Carlson M. N-terminal mutations modulate yeast SNF1 protein kinase function. Genetics. 1992;132: 639–650. 1468623

9. McCartney RR, Schmidt MC. Regulation of Snf1 kinase. Activation requires phosphorylation of threonine 210 by an upstream kinase as well as a distinct step mediated by the Snf4 subunit. J Biol Chem. 2001;276: 36460–36406. 11486005

10. Nath N, McCartney RR, Schmidt MC. Yeast Pak1 kinase associates with and activates Snf1. Mol Cell Biol. 2003;23: 3909–3917. 12748292

11. Hong SP, Leiper FC, Woods A, Carling D, Carlson M. Activation of yeast Snf1 and mammalian AMP-activated protein kinase by upstream kinases. Proc Natl Acad Sci U S A. 2003;100: 8839–8843. 12847291

12. Sutherland CM, Hawley SA, McCartney RR, Leech A, Stark MJ, Schmidt MC, et al. Elm1p is one of three upstream kinases for the Saccharomyces cerevisiae SNF1 complex. Curr Biol. 2003;13: 1299–1305. 12906789

13. Tu J, Carlson M. REG1 binds to protein phosphatase type 1 and regulates glucose repression in Saccharomyces cerevisiae. EMBO J. 1995;14: 5939–5946. 8846786

14. Sanz P, Alms GR, Haystead TA, Carlson M. Regulatory interactions between the Reg1-Glc7 protein phosphatase and the Snf1 protein kinase. Mol Cell Biol. 2000;20: 1321–1328. 10648618

15. Hong SP, Carlson M. Regulation of Snf1 protein kinase in response to environmental stress. J Biol Chem. 2007;282: 16838–16845. 17438333

16. Saito H, Posas F. Response to hyperosmotic stress. Genetics. 2012;192: 289–318. doi: 10.1534/genetics.112.140863 23028184

17. Brewster JL, Gustin MC. Hog1: 20 years of discovery and impact. Sci Signal. 2014;7: re7. doi: 10.1126/scisignal.2005458 25227612

18. Bicknell AA, Tourtellotte J, Niwa M. Late phase of the endoplasmic reticulum stress response pathway is regulated by Hog1 MAP kinase. J Biol Chem. 2010;285: 17545–17555. doi: 10.1074/jbc.M109.084681 20382742

19. Torres-Quiroz F, García-Marqués S, Coria R, Randez-Gil F, Prieto JA. The activity of yeast Hog1 MAPK is required during endoplasmic reticulum stress induced by tunicamycin exposure. J Biol Chem. 2010;285: 20088–20096. doi: 10.1074/jbc.M109.063578 20430884

20. Feng ZH, Wilson SE, Peng ZY, Schlender KK, Reimann EM, Trumbly RJ. The yeast GLC7 gene required for glycogen accumulation encodes a type 1 protein phosphatase. J Biol Chem. 1991;266: 23796–23801. 1660885

21. Cannon JF, Pringle JR, Fiechter A, Khalil M. Characterization of glycogen-deficient glc mutants of Saccharomyces cerevisiae. Genetics. 1994;136: 485–503. 8150278

22. Tatebayashi K, Takekawa M, Saito H. A docking site determining specificity of Pbs2 MAPKK for Ssk2/Ssk22 MAPKKKs in the yeast HOG pathway. EMBO J. 2003;22: 3624–3634. 12853477

23. Kyriakis JM, Avruch J. Mammalian MAPK signal transduction pathways activated by stress and inflammation: a 10-year update. Physiol Rev. 2012;92: 689–737. doi: 10.1152/physrev.00028.2011 22535895

24. Wurgler-Murphy SM, Maeda T, Witten EA, Saito H. Regulation of the Saccharomyces cerevisiae HOG1 mitogen-activated protein kinase by the PTP2 and PTP3 protein tyrosine phosphatases. Mol Cell Biol. 1997;17: 1289–1297. 9032256

25. Jacoby T, Flanagan H, Faykin A, Seto AG, Mattison C, Ota I. Two protein-tyrosine phosphatases inactivate the osmotic stress response pathway in yeast by targeting the mitogen-activated protein kinase, Hog1. J Biol Chem. 1997;272: 17749–17755. 9211927

26. Maeda T, Wurgler-Murphy SM, Saito H. A two-component system that regulates an osmosensing MAP kinase cascade in yeast. Nature. 1994;369: 242–245. 8183345

27. Maeda T, Takekawa M, Saito H. Activation of yeast PBS2 MAPKK by MAPKKKs or by binding of an SH3-containing osmosensor. Science. 1995;269: 554–558. 7624781

28. Ferrer-Dalmau J, Randez-Gil F, Marquina M, Prieto JA, Casamayor A. Protein kinase Snf1 is involved in the proper regulation of the unfolded protein response in Saccharomyces cerevisiae. Biochem J. 2015;468: 33–47. doi: 10.1042/BJ20140734 25730376

29. Mattison CP, Spencer SS, Kresge KA, Lee J, Ota IM. Differential regulation of the cell wall integrity mitogen-activated protein kinase pathway in budding yeast by the protein tyrosine phosphatases Ptp2 and Ptp3. Mol Cell Biol. 1999;19: 7651–760. 10523653

30. Chawla A, Chakrabarti S, Ghosh G, Niwa M. Attenuation of yeast UPR is essential for survival and is mediated by IRE1 kinase. J Cell Biol. 2011;193: 41–50. doi: 10.1083/jcb.201008071 21444691

31. Rubio C, Pincus D, Korennykh A, Schuck S, El-Samad H, Walter P. Homeostatic adaptation to endoplasmic reticulum stress depends on Ire1 kinase activity. J Cell Biol. 2011;193: 171–184. doi: 10.1083/jcb.201007077 21444684

32. Mizuno T, Hisamoto N, Terada T, Kondo T, Adachi M, Nishida E, et al. The Caenorhabditis elegans MAPK phosphatase VHP-1 mediates a novel JNK-like signaling pathway in stress response. EMBO J. 2004;23: 2226–2234. 15116070

33. Maeda T, Tsai AY, Saito H. Mutations in a protein tyrosine phosphatase gene (PTP2) and a protein serine/threonine phosphatase gene (PTC1) cause a synthetic growth defect in Saccharomyces cerevisiae. Mol Cell Biol. 1993;13: 5408–5417. 8395005

34. Gerwins P, Blank JL, Johnson GL. Cloning of a novel mitogen-activated protein kinase kinase kinase, MEKK4, that selectively regulates the c-Jun amino terminal kinase pathway. J Biol Chem. 1997;272: 8288–8295. 9079650

35. Takekawa M, Posas F, Saito H. A human homolog of the yeast Ssk2/Ssk22 MAP kinase kinase kinases, MTK1, mediates stress-induced activation of the p38 and JNK pathways. EMBO J. 1997;16: 4973–4982. 9305639

36. Takekawa M, Saito H. A family of stress-inducible GADD45-like proteins mediate activation of the stress-responsive MTK1/MEKK4 MAPKKK. Cell. 1998;95: 521–530. 9827804

37. Horie T, Tatebayashi K, Yamada R, Saito H. Phosphorylated Ssk1 prevents unphosphorylated Ssk1 from activating the Ssk2 mitogen-activated protein kinase kinase kinase in the yeast high-osmolarity glycerol osmoregulatory pathway. Mol Cell Biol. 2008;28: 5172–5183. doi: 10.1128/MCB.00589-08 18573873

38. Longtine MS, McKenzie A 3rd, Demarini DJ, Shah NG, Wach A, Brachat A, et al. Additional modules for versatile and economical PCR-based gene deletion and modification in Saccharomyces cerevisiae. Yeast. 1998;14: 953–961. 9717241

39. Kaiser CA, Adams A, Gottschling DE. Methods in yeast genetics. Cold Spring Harbor Laboratory Press: Cold Spring Harbor, NY; 1994.

40. Orlova M, Barrett L, Kuchin S. Detection of endogenous Snf1 and its activation state: application to Saccharomyces and Candida species. Yeast. 2008;25: 745–754. doi: 10.1002/yea.1628 18949820

41. Kushnirov VV. Rapid and reliable protein extraction from yeast. Yeast. 2000;16: 857–860. 10861908