Cell signaling regulates several physiological processes by receiving, processing, and transmitting signals between the extracellular and intracellular environments. In signal transduction, phosphorylation is a crucial effector as the most common posttranslational modification. Selectively recognizing specific phosphorylated motifs of target proteins and modulating their functions through binding interactions, the yeast 14-3-3 proteins Bmh1 and Bmh2 are involved in catabolite repression, carbon metabolism, endocytosis, and mitochondrial retrograde signaling, among other key cellular processes. These conserved scaffolding molecules also mediate crosstalk between ubiquitination and phosphorylation, the spatiotemporal control of meiosis, and the activity of ion transporters Trk1 and Nha1. In humans, deregulation of analogous processes triggers the development of serious diseases, such as diabetes, cancer, viral infections, microbial conditions and neuronal and age-related diseases. Accordingly, the aim of this review article is to provide a brief overview of the latest findings on the functions of yeast 14-3-3 proteins, focusing on their role in modulating the aforementioned processes.

Department of Physical and Macromolecular Chemistry Faculty of Science Charles University Prague Czechia

Institute of Physiology of the Czech Academy of Sciences Laboratory of Structural Biology of Signaling Proteins Division BIOCEV Vestec Czechia

Zobrazit více v PubMed

Alblova M., Smidova A., Docekal V., Vesely J., Herman P., Obsilova V., et al. (2017). Molecular basis of the 14-3-3 protein-dependent activation of yeast neutral trehalase Nth1. Proc. Natl. Acad. Sci. U. S. A. 114 (46), E9811–E9820. 10.1073/pnas.1714491114 PubMed DOI PMC

Alvaro C. G., Aindow A., Thorner J. (2016). Differential phosphorylation provides a switch to control how α-arrestin Rod1 down-regulates mating pheromone response in Saccharomyces cerevisiae . Genetics 203 (1), 299–317. 10.1534/genetics.115.186122 PubMed DOI PMC

Andoh T., Hirata Y., Kikuchi A. (2002). PY motifs of Rod1 are required for binding to Rsp5 and for drug resistance. FEBS Lett. 525 (1-3), 131–134. 10.1016/s0014-5793(02)03104-6 PubMed DOI

Arino J., Ramos J., Sychrova H. (2010). Alkali metal cation transport and homeostasis in yeasts. Microbiol. Mol. Biol. Rev. 74(1), 95–120. 10.1128/Mmbr.00042-09 PubMed DOI PMC

Arino J., Ramos J., Sychrova H. (2019). Monovalent cation transporters at the plasma membrane in yeasts. Yeast 36 (4), 177–193. 10.1002/yea.3355 PubMed DOI

Avecilla G., Spealman P., Matthews J., Caudal E., Schacherer J., Gresham D. (2023). Copy number variation alters local and global mutational tolerance. Genome Res. 33 (8), 1340–1353. 10.1101/gr.277625.122 PubMed DOI PMC

Ballew O., Lacefield S. (2019). The DNA damage checkpoint and the spindle position checkpoint maintain meiotic commitment in Saccharomyces cerevisiae . Curr. Biol. 29 (3), 449–460. 10.1016/j.cub.2018.12.043 PubMed DOI PMC

Beck T., Hall M. N. (1999). The TOR signalling pathway controls nuclear localization of nutrient-regulated transcription factors. Nature 402 (6762), 689–692. 10.1038/45287 PubMed DOI

Becuwe M., Herrador A., Haguenauer-Tsapis R., Vincent O., Leon S. (2012a). Ubiquitin-mediated regulation of endocytosis by proteins of the arrestin family. Biochem. Res. Int. 2012, 242764. 10.1155/2012/242764 PubMed DOI PMC

Becuwe M., Leon S. (2014). Integrated control of transporter endocytosis and recycling by the arrestin-related protein Rod1 and the ubiquitin ligase Rsp5. Elife 3, e03307. 10.7554/eLife.03307 PubMed DOI PMC

Becuwe M., Vieira N., Lara D., Gomes-Rezende J., Soares-Cunha C., Casal M., et al. (2012b). A molecular switch on an arrestin-like protein relays glucose signaling to transporter endocytosis. J. Cell. Biol. 196 (2), 247–259. 10.1083/jcb.201109113 PubMed DOI PMC

Belgareh-Touze N., Leon S., Erpapazoglou Z., Stawiecka-Mirota M., Urban-Grimal D., Haguenauer-Tsapis R. (2008). Versatile role of the yeast ubiquitin ligase Rsp5p in intracellular trafficking. Biochem. Soc. Trans. 36 (Pt 5), 791–796. 10.1042/BST0360791 PubMed DOI

Bendrioua L., Smedh M., Almquist J., Cvijovic M., Jirstrand M., Goksor M., et al. (2014). Yeast AMP-activated protein kinase monitors glucose concentration changes and absolute glucose levels. J. Biol. Chem. 289 (18), 12863–12875. 10.1074/jbc.M114.547976 PubMed DOI PMC

Berchowitz L. E., Kabachinski G., Walker M. R., Carlile T. M., Gilbert W. V., Schwartz T. U., et al. (2015). Regulated Formation of an amyloid-like translational repressor governs gametogenesis. Cell. 163 (2), 406–418. 10.1016/j.cell.2015.08.060 PubMed DOI PMC

Bertram P. G., Zeng C., Thorson J., Shaw A. S., Zheng X. F. (1998). The 14-3-3 proteins positively regulate rapamycin-sensitive signaling. Curr. Biol. 8 (23), 1259–1267. 10.1016/s0960-9822(07)00535-0 PubMed DOI

Braun K. A., Parua P. K., Dombek K. M., Miner G. E., Young E. T. (2013). 14-3-3 (Bmh) proteins regulate combinatorial transcription following RNA polymerase II recruitment by binding at Adr1-dependent promoters in Saccharomyces cerevisiae . Mol. Cell. Biol. 33 (4), 712–724. 10.1128/MCB.01226-12 PubMed DOI PMC

Braun K. A., Vaga S., Dombek K. M., Fang F., Palmisano S., Aebersold R., et al. (2014). Phosphoproteomic analysis identifies proteins involved in transcription-coupled mRNA decay as targets of Snf1 signaling. Sci. Signal 7 (333), ra64. 10.1126/scisignal.2005000 PubMed DOI

Bruckmann A., Steensma H. Y., Teixeira De Mattos M. J., Van Heusden G. P. (2004). Regulation of transcription by Saccharomyces cerevisiae 14-3-3 proteins. Biochem. J. 382 (Pt 3), 867–875. 10.1042/BJ20031885 PubMed DOI PMC

Bui T. H. D., Labedzka-Dmoch K. (2023). RetroGREAT signaling: the lessons we learn from yeast. IUBMB Life 76, 26–37. 10.1002/iub.2775 PubMed DOI

Butow R. A., Avadhani N. G. (2004). Mitochondrial signaling: the retrograde response. Mol. Cell. 14 (1), 1–15. 10.1016/s1097-2765(04)00179-0 PubMed DOI

Carlson M. (1999). Glucose repression in yeast. Curr. Opin. Microbiol. 2 (2), 202–207. 10.1016/S1369-5274(99)80035-6 PubMed DOI

Carpenter K., Bell R. B., Yunus J., Amon A., Berchowitz L. E. (2018). Phosphorylation-mediated clearance of amyloid-like assemblies in meiosis. Dev. Cell. 45 (3), 392–405. 10.1016/j.devcel.2018.04.001 PubMed DOI PMC

Castillo K., Nassif M., Valenzuela V., Rojas F., Matus S., Mercado G., et al. (2013). Trehalose delays the progression of amyotrophic lateral sclerosis by enhancing autophagy in motoneurons. Autophagy 9 (9), 1308–1320. 10.4161/auto.25188 PubMed DOI

Chaudhri M., Scarabel M., Aitken A. (2003). Mammalian and yeast 14-3-3 isoforms form distinct patterns of dimers in vivo . Biochem. Biophys. Res. Commun. 300 (3), 679–685. 10.1016/s0006-291x(02)02902-9 PubMed DOI

Chen Y., Liang J., Chen Z., Wang B., Si T. (2021). Genome-scale screening and combinatorial optimization of gene overexpression targets to improve cadmium tolerance in Saccharomyces cerevisiae . Front. Microbiol. 12, 662512. 10.3389/fmicb.2021.662512 PubMed DOI PMC

Chiu S. T., Tseng W. W., Wei A. C. (2022). Mathematical modeling and analysis of mitochondrial retrograde signaling dynamics. iScience 25 (12), 105502. 10.1016/j.isci.2022.105502 PubMed DOI PMC

Clapp C., Portt L., Khoury C., Sheibani S., Eid R., Greenwood M., et al. (2012a). Untangling the roles of anti-apoptosis in regulating programmed cell death using humanized yeast cells. Front. Oncol. 2, 59. 10.3389/fonc.2012.00059 PubMed DOI PMC

Clapp C., Portt L., Khoury C., Sheibani S., Norman G., Ebner P., et al. (2012b). 14-3-3 protects against stress-induced apoptosis. Cell. Death Dis. 3 (7), e348. 10.1038/cddis.2012.90 PubMed DOI PMC

Cognetti D., Davis D., Sturtevant J. (2002). The Candida albicans 14-3-3 gene, BMH1, is essential for growth. Yeast 19 (1), 55–67. 10.1002/yea.804 PubMed DOI

Conrad M., Schothorst J., Kankipati H. N., Van Zeebroeck G., Rubio-Texeira M., Thevelein J. M. (2014). Nutrient sensing and signaling in the yeast Saccharomyces cerevisiae . FEMS Microbiol. Rev. 38 (2), 254–299. 10.1111/1574-6976.12065 PubMed DOI PMC

Crowe J. H., Crowe L. M., Chapman D. (1984). Preservation of membranes in anhydrobiotic organisms: the role of trehalose. Science 223 (4637), 701–703. 10.1126/science.223.4637.701 PubMed DOI

Dengler L., Ord M., Schwab L. M., Loog M., Ewald J. C. (2021). Regulation of trehalase activity by multi-site phosphorylation and 14-3-3 interaction. Sci. Rep. 11 (1), 962. 10.1038/s41598-020-80357-3 PubMed DOI PMC

De Virgilio C., Burckert N., Bell W., Jeno P., Boller T., Wiemken A. (1993). Disruption of TPS2, the gene encoding the 100-kDa subunit of the trehalose-6-phosphate synthase/phosphatase complex in Saccharomyces cerevisiae, causes accumulation of trehalose-6-phosphate and loss of trehalose-6-phosphate phosphatase activity. Eur. J. Biochem. 212 (2), 315–323. 10.1111/j.1432-1033.1993.tb17664.x PubMed DOI

De Vit M. J., Waddle J. A., Johnston M. (1997). Regulated nuclear translocation of the Mig1 glucose repressor. Mol. Biol. Cell. 8 (8), 1603–1618. 10.1091/mbc.8.8.1603 PubMed DOI PMC

Dombek K. M., Kacherovsky N., Young E. T. (2004). The Reg1-interacting proteins, Bmh1, Bmh2, Ssb1, and Ssb2, have roles in maintaining glucose repression in Saccharomyces cerevisiae . J. Biol. Chem. 279 (37), 39165–39174. 10.1074/jbc.M400433200 PubMed DOI

Eid R., Zhou D. R., Arab N. T. T., Boucher E., Young P. G., Mandato C. A., et al. (2017). Heterologous expression of anti-apoptotic human 14-3-3β/α enhances iron-mediated programmed cell death in yeast. PLoS One 12 (8), e0184151. 10.1371/journal.pone.0184151 PubMed DOI PMC

Eisenreichova A., Klima M., Boura E. (2016). Crystal structures of a yeast 14-3-3 protein from Lachancea thermotolerans in the unliganded form and bound to a human lipid kinase PI4KB-derived peptide reveal high evolutionary conservation. Acta Crystallogr. Sect. F. Struct. Biol. Commun. 72 (Pt 11), 799–803. 10.1107/S2053230X16015053 PubMed DOI PMC

Elbing K., McCartney R. R., Schmidt M. C. (2006). Purification and characterization of the three Snf1-activating kinases of Saccharomyces cerevisiae . Biochem. J. 393 (Pt 3), 797–805. 10.1042/BJ20051213 PubMed DOI PMC

Enyenihi A. H., Saunders W. S. (2003). Large-scale functional genomic analysis of sporulation and meiosis in Saccharomyces cerevisiae . Genetics 163 (1), 47–54. 10.1093/genetics/163.1.47 PubMed DOI PMC

Esposito R. E., Esposito M. S. (1974). Genetic recombination and commitment to meiosis in Saccharomyces. Proc. Natl. Acad. Sci. U. S. A. 71 (8), 3172–3176. 10.1073/pnas.71.8.3172 PubMed DOI PMC

Ewald J. C. (2018). How yeast coordinates metabolism, growth and division. Curr. Opin. Microbiol. 45, 1–7. 10.1016/j.mib.2017.12.012 PubMed DOI

Ewald J. C., Kuehne A., Zamboni N., Skotheim J. M. (2016). The yeast cyclin-dependent kinase routes carbon fluxes to fuel cell cycle progression. Mol. Cell. 62 (4), 532–545. 10.1016/j.molcel.2016.02.017 PubMed DOI PMC

Feng W., Arguello-Miranda O., Qian S., Wang F. (2022). Cdc14 spatiotemporally dephosphorylates Atg13 to activate autophagy during meiotic divisions. J. Cell. Biol. 221 (5), e202107151. 10.1083/jcb.202107151 PubMed DOI PMC

Ford J. C., al-Khodairy F., Fotou E., Sheldrick K. S., Griffiths D. J., Carr A. M. (1994). 14-3-3 protein homologs required for the DNA damage checkpoint in fission yeast. Science 265 (5171), 533–535. 10.1126/science.8036497 PubMed DOI

Gancedo J. M. (1998). Yeast carbon catabolite repression. Microbiol. Mol. Biol. Rev. 62 (2), 334–361. 10.1128/MMBR.62.2.334-361.1998 PubMed DOI PMC

Ganguly S., Weller J. L., Ho A., Chemineau P., Malpaux B., Klein D. C. (2005). Melatonin synthesis: 14-3-3-dependent activation and inhibition of arylalkylamine N-acetyltransferase mediated by phosphoserine-205. Proc. Natl. Acad. Sci. U. S. A. 102 (4), 1222–1227. 10.1073/pnas.0406871102 PubMed DOI PMC

Gavade J. N., Puccia C. M., Herod S. G., Trinidad J. C., Berchowitz L. E., Lacefield S. (2022). Identification of 14-3-3 proteins, Polo kinase, and RNA-binding protein Pes4 as key regulators of meiotic commitment in budding yeast. Curr. Biol. 32 (7), 1534–1547.e9. 10.1016/j.cub.2022.02.022 PubMed DOI PMC

Gerbich T. M., Gladfelter A. S. (2021). Moving beyond disease to function: physiological roles for polyglutamine-rich sequences in cell decisions. Curr. Opin. Cell. Biol. 69, 120–126. 10.1016/j.ceb.2021.01.003 PubMed DOI

Gonzalez B., Mirzaei M., Basu S., Pujari A. N., Vandermeulen M. D., Prabhakar A., et al. (2023). Turnover and bypass of p21-activated kinase during Cdc42-dependent MAPK signaling in yeast. J. Biol. Chem. 299 (11), 105297. 10.1016/j.jbc.2023.105297 PubMed DOI PMC

Herod S. G., Dyatel A., Hodapp S., Jovanovic M., Berchowitz L. E. (2022). Clearance of an amyloid-like translational repressor is governed by 14-3-3 proteins. Cell. Rep. 39 (5), 110753. 10.1016/j.celrep.2022.110753 PubMed DOI PMC

Hinnebusch A. G. (2005). Translational regulation of GCN4 and the general amino acid control of yeast. Annu. Rev. Microbiol. 59, 407–450. 10.1146/annurev.micro.59.031805.133833 PubMed DOI

Horak J. (2013). Regulations of sugar transporters: insights from yeast. Curr. Genet. 59 (1-2), 1–31. 10.1007/s00294-013-0388-8 PubMed DOI

Horvath M., Petrvalska O., Herman P., Obsilova V., Obsil T. (2021). 14-3-3 proteins inactivate DAPK2 by promoting its dimerization and protecting key regulatory phosphosites. Commun. Biol. 4 (1), 986. 10.1038/s42003-021-02518-y PubMed DOI PMC

Hovsepian J., Defenouillere Q., Albanese V., Vachova L., Garcia C., Palkova Z., et al. (2017). Multilevel regulation of an α-arrestin by glucose depletion controls hexose transporter endocytosis. J. Cell. Biol. 216 (6), 1811–1831. 10.1083/jcb.201610094 PubMed DOI PMC

Hubscher V., Mudholkar K., Chiabudini M., Fitzke E., Wolfle T., Pfeifer D., et al. (2016). The Hsp70 homolog Ssb and the 14-3-3 protein Bmh1 jointly regulate transcription of glucose repressed genes in Saccharomyces cerevisiae . Nucleic Acids Res. 44 (12), 5629–5645. 10.1093/nar/gkw168 PubMed DOI PMC

Hubscher V., Mudholkar K., Rospert S. (2017). The yeast Hsp70 homolog Ssb: a chaperone for general de novo protein folding and a nanny for specific intrinsically disordered protein domains. Curr. Genet. 63 (1), 9–13. 10.1007/s00294-016-0610-6 PubMed DOI PMC

Hurtado C. A. R., Rachubinski R. A. (2002). YlBMH1 encodes a 14-3-3 protein that promotes filamentous growth in the dimorphic yeast Yarrowia lipolytica. Microbiol. Read. 148 (Pt 11), 3725–3735. 10.1099/00221287-148-11-3725 PubMed DOI

Ichimura T., Kubota H., Goma T., Mizushima N., Ohsumi Y., Iwago M., et al. (2004). Transcriptomic and proteomic analysis of a 14-3-3 gene-deficient yeast. Biochemistry 43 (20), 6149–6158. 10.1021/bi035421i PubMed DOI

Jin L., Zhang K., Sternglanz R., Neiman A. M. (2017). Predicted RNA binding proteins Pes4 and Mip6 regulate mRNA levels, translation, and localization during sporulation in budding yeast. Mol. Cell. Biol. 37 (9), e00408-16. 10.1128/MCB.00408-16 PubMed DOI PMC

Kakiuchi K., Yamauchi Y., Taoka M., Iwago M., Fujita T., Ito T., et al. (2007). Proteomic analysis of in vivo 14-3-3 interactions in the yeast Saccharomyces cerevisiae . Biochemistry 46 (26), 7781–7792. 10.1021/bi700501t PubMed DOI

Kalabova D., Filandr F., Alblova M., Petrvalska O., Horvath M., Man P., et al. (2020). 14-3-3 protein binding blocks the dimerization interface of caspase-2. FEBS J. 287 (16), 3494–3510. 10.1111/febs.15215 PubMed DOI

Kim B., Lee Y., Choi H., Huh W. K. (2021). The trehalose-6-phosphate phosphatase Tps2 regulates ATG8 transcription and autophagy in Saccharomyces cerevisiae . Autophagy 17 (4), 1013–1027. 10.1080/15548627.2020.1746592 PubMed DOI PMC

Kinclova O., Ramos J., Potier S., Sychrova H. (2001). Functional study of the Saccharomyces cerevisiae Nha1p C-terminus. Mol. Microbiol. 40 (3), 656–668. 10.1046/j.1365-2958.2001.02412.x PubMed DOI

King O. D., Gitler A. D., Shorter J. (2012). The tip of the iceberg: RNA-binding proteins with prion-like domains in neurodegenerative disease. Brain Res. 1462, 61–80. 10.1016/j.brainres.2012.01.016 PubMed DOI PMC

Kleppe R., Martinez A., Doskeland S. O., Haavik J. (2011). The 14-3-3 proteins in regulation of cellular metabolism. Semin. Cell. Dev. Biol. 22 (7), 713–719. 10.1016/j.semcdb.2011.08.008 PubMed DOI

Knowles T. P., Vendruscolo M., Dobson C. M. (2014). The amyloid state and its association with protein misfolding diseases. Nat. Rev. Mol. Cell. Biol. 15 (6), 384–396. 10.1038/nrm3810 PubMed DOI

Kopecka M., Kosek D., Kukacka Z., Rezabkova L., Man P., Novak P., et al. (2014). Role of the EF-hand-like motif in the 14-3-3 protein-mediated activation of yeast neutral trehalase Nth1. J. Biol. Chem. 289 (20), 13948–13961. 10.1074/jbc.M113.544551 PubMed DOI PMC

Kulkarni A., Buford T. D., Rai R., Cooper T. G. (2006). Differing responses of Gat1 and Gln3 phosphorylation and localization to rapamycin and methionine sulfoximine treatment in Saccharomyces cerevisiae . FEMS Yeast Res. 6 (2), 218–229. 10.1111/j.1567-1364.2006.00031.x PubMed DOI PMC

Kumar R. (2017). An account of fungal 14-3-3 proteins. Eur. J. Cell. Biol. 96 (2), 206–217. 10.1016/j.ejcb.2017.02.006 PubMed DOI

Kumar R., Srivastava S. (2016). Quantitative proteomic comparison of stationary/G0 phase cells and tetrads in budding yeast. Sci. Rep. 6, 32031. 10.1038/srep32031 PubMed DOI PMC

Latz A., Becker D., Hekman M., Mueller T., Beyhl D., Marten I., et al. (2007). TPK1, a Ca2+-regulated Arabidopsis vacuole two-pore K+ channel is activated by 14-3-3 proteins. Plant J. 52 (3), 449–459. 10.1111/j.1365-313X.2007.03255.x PubMed DOI

Lehoux S., Abe J., Florian J. A., Berk B. C. (2001). 14-3-3 Binding to Na+/H+ exchanger isoform-1 is associated with serum-dependent activation of Na+/H+ exchange. J. Biol. Chem. 276 (19), 15794–15800. 10.1074/jbc.M100410200 PubMed DOI

Liu D., Bienkowska J., Petosa C., Collier R. J., Fu H., Liddington R. (1995). Crystal structure of the zeta isoform of the 14-3-3 protein. Nature 376 (6536), 191–194. 10.1038/376191a0 PubMed DOI

Liu Z., Butow R. A. (2006). Mitochondrial retrograde signaling. Annu. Rev. Genet. 40, 159–185. 10.1146/annurev.genet.40.110405.090613 PubMed DOI

Liu Z., Sekito T., Epstein C. B., Butow R. A. (2001). RTG-dependent mitochondria to nucleus signaling is negatively regulated by the seven WD-repeat protein Lst8p. EMBO J. 20 (24), 7209–7219. 10.1093/emboj/20.24.7209 PubMed DOI PMC

Liu Z., Spirek M., Thornton J., Butow R. A. (2005). A novel degron-mediated degradation of the RTG pathway regulator, Mks1p, by SCFGrr1. Mol. Biol. Cell. 16 (10), 4893–4904. 10.1091/mbc.e05-06-0516 PubMed DOI PMC

Llopis-Torregrosa V., Ferri-Blazquez A., Adam-Artigues A., Deffontaines E., van Heusden G. P., Yenush L. (2016). Regulation of the yeast Hxt6 hexose transporter by the Rod1 α-arrestin, the Snf1 protein kinase, and the Bmh2 14-3-3 protein. J. Biol. Chem. 291 (29), 14973–14985. 10.1074/jbc.M116.733923 PubMed DOI PMC

Macakova E., Kopecka M., Kukacka Z., Veisova D., Novak P., Man P., et al. (2013). Structural basis of the 14-3-3 protein-dependent activation of yeast neutral trehalase Nth1. Biochim. Biophys. Acta 1830 (10), 4491–4499. 10.1016/j.bbagen.2013.05.025 PubMed DOI

MacGurn J. A., Hsu P. C., Emr S. D. (2012). Ubiquitin and membrane protein turnover: from cradle to grave. Annu. Rev. Biochem. 81, 231–259. 10.1146/annurev-biochem-060210-093619 PubMed DOI

MacGurn J. A., Hsu P. C., Smolka M. B., Emr S. D. (2011). TORC1 regulates endocytosis via Npr1-mediated phosphoinhibition of a ubiquitin ligase adaptor. Cell. 147 (5), 1104–1117. 10.1016/j.cell.2011.09.054 PubMed DOI

Madrid R., Gomez M. J., Ramos J., Rodriguez-Navarro A. (1998). Ectopic potassium uptake in trk1 trk2 mutants of Saccharomyces cerevisiae correlates with a highly hyperpolarized membrane potential. J. Biol. Chem. 273 (24), 14838–14844. 10.1074/jbc.273.24.14838 PubMed DOI

Masaryk J., Kale D., Pohl P., Ruiz-Castilla F. J., Zimmermannova O., Obsilova V., et al. (2023). The second intracellular loop of the yeast Trk1 potassium transporter is involved in regulation of activity, and interaction with 14-3-3 proteins. Comput. Struct. Biotechnol. J. 21, 2705–2716. 10.1016/j.csbj.2023.04.019 PubMed DOI PMC

Mayordomo I., Regelmann J., Horak J., Sanz P. (2003). Saccharomyces cerevisiae 14-3-3 proteins Bmh1 and Bmh2 participate in the process of catabolite inactivation of maltose permease. FEBS Lett. 544 (1-3), 160–164. 10.1016/s0014-5793(03)00498-8 PubMed DOI

Merhi A., Andre B. (2012). Internal amino acids promote Gap1 permease ubiquitylation via TORC1/Npr1/14-3-3-dependent control of the Bul arrestin-like adaptors. Mol. Cell. Biol. 32 (22), 4510–4522. 10.1128/MCB.00463-12 PubMed DOI PMC

Obsil T., Ghirlando R., Anderson D. E., Hickman A. B., Dyda F. (2003). Two 14-3-3 binding motifs are required for stable association of Forkhead transcription factor FOXO4 with 14-3-3 proteins and inhibition of DNA binding. Biochemistry 42 (51), 15264–15272. 10.1021/bi0352724 PubMed DOI

Obsil T., Ghirlando R., Klein D. C., Ganguly S., Dyda F. (2001). Crystal structure of the 14-3-3zeta:serotonin N-acetyltransferase complex. a role for scaffolding in enzyme regulation. Cell. 105 (2), 257–267. 10.1016/s0092-8674(01)00316-6 PubMed DOI

Obsilova V., Herman P., Vecer J., Sulc M., Teisinger J., Obsil T. (2004). 14-3-3zeta C-terminal stretch changes its conformation upon ligand binding and phosphorylation at Thr232. J. Biol. Chem. 279 (6), 4531–4540. 10.1074/jbc.M306939200 PubMed DOI

Obsilova V., Kopecka M., Kosek D., Kacirova M., Kylarova S., Rezabkova L., et al. (2014). Mechanisms of the 14-3-3 protein function: regulation of protein function through conformational modulation. Physiol. Res. 63 (Suppl. 1), S155–S164. 10.33549/physiolres.932659 PubMed DOI

Obsilova V., Obsil T. (2022). Structural insights into the functional roles of 14-3-3 proteins. Front. Mol. Biosci. 9, 1016071. 10.3389/fmolb.2022.1016071 PubMed DOI PMC

Ottmann C., Marco S., Jaspert N., Marcon C., Schauer N., Weyand M., et al. (2007). Structure of a 14-3-3 coordinated hexamer of the plant plasma membrane H+ -ATPase by combining X-ray crystallography and electron cryomicroscopy. Mol. Cell. 25 (3), 427–440. 10.1016/j.molcel.2006.12.017 PubMed DOI

Paiva S., Kruckeberg A. L., Casal M. (2002). Utilization of green fluorescent protein as a marker for studying the expression and turnover of the monocarboxylate permease Jen1p of Saccharomyces cerevisiae . Biochem. J. 363 (Pt 3), 737–744. 10.1042/0264-6021:3630737 PubMed DOI PMC

Panni S., Landgraf C., Volkmer-Engert R., Cesareni G., Castagnoli L. (2008). Role of 14-3-3 proteins in the regulation of neutral trehalase in the yeast Saccharomyces cerevisiae . FEMS Yeast Res. 8 (1), 53–63. 10.1111/j.1567-1364.2007.00312.x PubMed DOI

Parua P. K., Ratnakumar S., Braun K. A., Dombek K. M., Arms E., Ryan P. M., et al. (2010). 14-3-3 (Bmh) proteins inhibit transcription activation by Adr1 through direct binding to its regulatory domain. Mol. Cell. Biol. 30 (22), 5273–5283. 10.1128/MCB.00715-10 PubMed DOI PMC

Parua P. K., Young E. T. (2014). Binding and transcriptional regulation by 14-3-3 (Bmh) proteins requires residues outside of the canonical motif. Eukaryot. Cell. 13 (1), 21–30. 10.1128/EC.00240-13 PubMed DOI PMC

Pedruzzi I., Dubouloz F., Cameroni E., Wanke V., Roosen J., Winderickx J., et al. (2003). TOR and PKA signaling pathways converge on the protein kinase Rim15 to control entry into G0. Mol. Cell. 12 (6), 1607–1613. 10.1016/s1097-2765(03)00485-4 PubMed DOI

Peisker K., Chiabudini M., Rospert S. (2010). The ribosome-bound Hsp70 homolog Ssb of Saccharomyces cerevisiae . Biochim. Biophys. Acta 1803 (6), 662–672. 10.1016/j.bbamcr.2010.03.005 PubMed DOI

Pohl P., Joshi R., Petrvalska O., Obsil T., Obsilova V. (2021). 14-3-3-protein regulates Nedd4-2 by modulating interactions between HECT and WW domains. Commun. Biol. 4 (1), 899. 10.1038/s42003-021-02419-0 PubMed DOI PMC

Polo S., Di Fiore P. P. (2008). Finding the right partner: science or ART? Cell. 135 (4), 590–592. 10.1016/j.cell.2008.10.032 PubMed DOI

Psenakova K., Petrvalska O., Kylarova S., Lentini Santo D., Kalabova D., Herman P., et al. (2018). 14-3-3 protein directly interacts with the kinase domain of calcium/calmodulin-dependent protein kinase kinase (CaMKK2). Biochim. Biophys. Acta 1862 (7), 1612–1625. 10.1016/j.bbagen.2018.04.006 PubMed DOI

Ratnakumar S., Kacherovsky N., Arms E., Young E. T. (2009). Snf1 controls the activity of adr1 through dephosphorylation of Ser230. Genetics 182 (3), 735–745. 10.1534/genetics.109.103432 PubMed DOI PMC

Ren L., Hou Y. P., Zhu Y. Y., Zhao F. F., Duan Y. B., Wu L. Y., et al. (2022). Validamycin A enhances the interaction between neutral trehalase and 14-3-3 protein Bmh1 in Fusarium graminearum. Phytopathology 112 (2), 290–298. 10.1094/PHYTO-05-21-0214-R PubMed DOI

Rial S. A., Shishani R., Cummings B. P., Lim G. E. (2023). Is 14-3-3 the combination to unlock new pathways to improve metabolic homeostasis and beta-cell function? Diabetes 72 (8), 1045–1054. 10.2337/db23-0094 PubMed DOI PMC

Rios-Anjos R. M., Camandona V. L., Bleicher L., Ferreira-Junior J. R. (2017). Structural and functional mapping of Rtg2p determinants involved in retrograde signaling and aging of Saccharomyces cerevisiae . PLoS One 12 (5), e0177090. 10.1371/journal.pone.0177090 PubMed DOI PMC

Ripaud L., Chumakova V., Antonin M., Hastie A. R., Pinkert S., Korner R., et al. (2014). Overexpression of Q-rich prion-like proteins suppresses polyQ cytotoxicity and alters the polyQ interactome. Proc. Natl. Acad. Sci. U. S. A. 111 (51), 18219–18224. 10.1073/pnas.1421313111 PubMed DOI PMC

Rittinger K., Budman J., Xu J., Volinia S., Cantley L. C., Smerdon S. J., et al. (1999). Structural analysis of 14-3-3 phosphopeptide complexes identifies a dual role for the nuclear export signal of 14-3-3 in ligand binding. Mol. Cell. 4 (2), 153–166. 10.1016/s1097-2765(00)80363-9 PubMed DOI

Rubenstein E. M., McCartney R. R., Zhang C., Shokat K. M., Shirra M. K., Arndt K. M., et al. (2008). Access denied: Snf1 activation loop phosphorylation is controlled by availability of the phosphorylated threonine 210 to the PP1 phosphatase. J. Biol. Chem. 283 (1), 222–230. 10.1074/jbc.M707957200 PubMed DOI PMC

Ruiz A., Arino J. (2007). Function and regulation of the Saccharomyces cerevisiae ENA sodium ATPase system. Eukaryot. Cell. 6 (12), 2175–2183. 10.1128/EC.00337-07 PubMed DOI PMC

Sarkar S., Davies J. E., Huang Z., Tunnacliffe A., Rubinsztein D. C. (2007). Trehalose, a novel mTOR-independent autophagy enhancer, accelerates the clearance of mutant huntingtin and alpha-synuclein. J. Biol. Chem. 282 (8), 5641–5652. 10.1074/jbc.M609532200 PubMed DOI

Schepers W., Van Zeebroeck G., Pinkse M., Verhaert P., Thevelein J. M. (2012). In vivo phosphorylation of Ser21 and Ser83 during nutrient-induced activation of the yeast protein kinase A (PKA) target trehalase. J. Biol. Chem. 287, 44130–44142. 10.1074/jbc.M112.421503 PubMed DOI PMC

Shinoda J., Kikuchi Y. (2007). Rod1, an arrestin-related protein, is phosphorylated by Snf1-kinase in Saccharomyces cerevisiae . Biochem. Biophys. Res. Commun. 364 (2), 258–263. 10.1016/j.bbrc.2007.09.134 PubMed DOI

Silhan J., Obsilova V., Vecer J., Herman P., Sulc M., Teisinger J., et al. (2004). 14-3-3 protein C-terminal stretch occupies ligand binding groove and is displaced by phosphopeptide binding. J. Biol. Chem. 279 (47), 49113–49119. 10.1074/jbc.M408671200 PubMed DOI

Sluchanko N. N., Gusev N. B. (2017). Moonlighting chaperone-like activity of the universal regulatory 14-3-3 proteins. FEBS J. 284 (9), 1279–1295. 10.1111/febs.13986 PubMed DOI

Smidova A., Stankova K., Petrvalska O., Lazar J., Sychrova H., Obsil T., et al. (2019). The activity of Saccharomyces cerevisiae Na(+), K(+)/H(+) antiporter Nha1 is negatively regulated by 14-3-3 protein binding at serine 481. Biochim. Biophys. Acta Mol. Cell. Res. 1866 (12), 118534. 10.1016/j.bbamcr.2019.118534 PubMed DOI

Solaki M., Ewald J. C. (2018). Fueling the cycle: CDKs in carbon and energy metabolism. Front. Cell. Dev. Biol. 6, 93. 10.3389/fcell.2018.00093 PubMed DOI PMC

Tate J. J., Buford D., Rai R., Cooper T. G. (2017). General amino acid control and 14-3-3 proteins bmh1/2 are required for nitrogen catabolite repression-sensitive regulation of Gln3 and Gat1 localization. Genetics 205 (2), 633–655. 10.1534/genetics.116.195800 PubMed DOI PMC

Thandavarayan R. A., Watanabe K., Ma M., Veeyaveedu P. T., Gurusamy N., Palaniyandi S. S., et al. (2008). 14-3-3 protein regulates Ask1 signaling and protects against diabetic cardiomyopathy. Biochem. Pharmacol. 75 (9), 1797–1806. 10.1016/j.bcp.2008.02.003 PubMed DOI

Trembley M. A., Berrus H. L., Whicher J. R., Humphrey-Dixon E. L. (2014). The yeast 14-3-3 proteins BMH1 and BMH2 differentially regulate rapamycin-mediated transcription. Biosci. Rep. 34 (2), e00099. 10.1042/BSR20130096 PubMed DOI PMC

Trendeleva T. A., Zvyagilskaya R. A. (2018). Retrograde signaling as a mechanism of yeast adaptation to unfavorable factors. Biochem. (Mosc) 83 (2), 98–106. 10.1134/S0006297918020025 PubMed DOI

Truong A. B., Masters S. C., Yang H., Fu H. (2002). Role of the 14-3-3 C-terminal loop in ligand interaction. Proteins 49 (3), 321–325. 10.1002/prot.10210 PubMed DOI

Tsuchiya D., Yang Y., Lacefield S. (2014). Positive feedback of NDT80 expression ensures irreversible meiotic commitment in budding yeast. PLoS Genet. 10 (6), e1004398. 10.1371/journal.pgen.1004398 PubMed DOI PMC

van Hemert M. J., van Heusden G. P., Steensma H. Y. (2001). Yeast 14-3-3 proteins. Yeast 18 (10), 889–895. 10.1002/yea.739 PubMed DOI

van Heusden G. P. (2005). 14-3-3 proteins: regulators of numerous eukaryotic proteins. IUBMB Life 57 (9), 623–629. 10.1080/15216540500252666 PubMed DOI

van Heusden G. P. (2009). 14-3-3 Proteins: insights from genome-wide studies in yeast. Genomics 94 (5), 287–293. 10.1016/j.ygeno.2009.07.004 PubMed DOI

van Heusden G. P., Griffiths D. J., Ford J. C., Chin A. W. T. F., Schrader P. A., Carr A. M., et al. (1995). The 14-3-3 proteins encoded by the BMH1 and BMH2 genes are essential in the yeast Saccharomyces cerevisiae and can be replaced by a plant homologue. Eur. J. Biochem. 229 (1), 45–53. 10.1111/j.1432-1033.1995.tb20435.x PubMed DOI

van Heusden G. P., Steensma H. Y. (2001). 14-3-3 Proteins are essential for regulation of RTG3-dependent transcription in Saccharomyces cerevisiae . Yeast 18 (16), 1479–1491. 10.1002/yea.765 PubMed DOI

van Heusden G. P., Wenzel T. J., Lagendijk E. L., de Steensma H. Y., van den Berg J. A. (1992). Characterization of the yeast BMH1 gene encoding a putative protein homologous to mammalian protein kinase II activators and protein kinase C inhibitors. FEBS Lett. 302 (2), 145–150. 10.1016/0014-5793(92)80426-h PubMed DOI

van Heusden G. P., Yde Steensma H. (2006). Yeast 14-3-3 proteins. Yeast 23 (3), 159–171. 10.1002/yea.1338 PubMed DOI

Veisova D., Macakova E., Rezabkova L., Sulc M., Vacha P., Sychrova H., et al. (2012). Role of individual phosphorylation sites for the 14-3-3-protein-dependent activation of yeast neutral trehalase Nth1. Biochem. J. 443 (3), 663–670. 10.1042/BJ20111615 PubMed DOI

Veisova D., Rezabkova L., Stepanek M., Novotna P., Herman P., Vecer J., et al. (2010). The C-terminal segment of yeast BMH proteins exhibits different structure compared to other 14-3-3 protein isoforms. Biochemistry 49 (18), 3853–3861. 10.1021/bi100273k PubMed DOI

Wang C., Skinner C., Easlon E., Lin S. J. (2009). Deleting the 14-3-3 protein Bmh1 extends life span in Saccharomyces cerevisiae by increasing stress response. Genetics 183 (4), 1373–1384. 10.1534/genetics.109.107797 PubMed DOI PMC

Watanabe K., Ma M., Narasimman G., Suresh P. S., Juan W., Punniyakoti V. T. (2008). P361 14-3-3 Protein prevents development of diabetic cardiomyopathy. Int. J. Cardiol. 125, S69. 10.1016/s0167-5273(08)70272-9 DOI

Wera S., De Schrijver E., Geyskens I., Nwaka S., Thevelein J. M. (1999). Opposite roles of trehalase activity in heat-shock recovery and heat-shock survival in Saccharomyces cerevisiae . Biochem. J. 343 Pt 3, 621–626. 10.1042/0264-6021:3430621 PubMed DOI PMC

Wollman A. J., Shashkova S., Hedlund E. G., Friemann R., Hohmann S., Leake M. C. (2017). Transcription factor clusters regulate genes in eukaryotic cells. Elife 6, e27451. 10.7554/eLife.27451 PubMed DOI PMC

Xiao B., Smerdon S. J., Jones D. H., Dodson G. G., Soneji Y., Aitken A., et al. (1995). Structure of a 14-3-3 protein and implications for coordination of multiple signalling pathways. Nature 376 (6536), 188–191. 10.1038/376188a0 PubMed DOI

Yaffe M. B., Rittinger K., Volinia S., Caron P. R., Aitken A., Leffers H., et al. (1997). The structural basis for 14-3-3:phosphopeptide binding specificity. Cell. 91 (7), 961–971. 10.1016/s0092-8674(00)80487-0 PubMed DOI

Yamada Y., Shiroma A., Hirai S., Iwasaki J. (2023). Zuo1, a ribosome-associated J protein, is involved in glucose repression in Saccharomyces cerevisiae . FEMS Yeast Res. 23, foad038. 10.1093/femsyr/foad038 PubMed DOI

Yang X., Lee W. H., Sobott F., Papagrigoriou E., Robinson C. V., Grossmann J. G., et al. (2006). Structural basis for protein-protein interactions in the 14-3-3 protein family. Proc. Natl. Acad. Sci. U. S. A. 103 (46), 17237–17242. 10.1073/pnas.0605779103 PubMed DOI PMC

Yasukawa T., Iwama R., Yamasaki Y., Masuo N., Noda Y. (2023). Yeast Rim11 kinase responds to glutathione-induced stress by regulating the transcription of phospholipid biosynthetic genes. Mol. Biol. Cell. 35, ar8. 10.1091/mbc.E23-03-0116 PubMed DOI PMC

Young E. T., Tachibana C., Chang H. W., Dombek K. M., Arms E. M., Biddick R. (2008). Artificial recruitment of mediator by the DNA-binding domain of Adr1 overcomes glucose repression of ADH2 expression. Mol. Cell. Biol. 28 (8), 2509–2516. 10.1128/MCB.00658-07 PubMed DOI PMC

Young E. T., Zhang C., Shokat K. M., Parua P. K., Braun K. A. (2012). The AMP-activated protein kinase Snf1 regulates transcription factor binding, RNA polymerase II activity, and mRNA stability of glucose-repressed genes in Saccharomyces cerevisiae . J. Biol. Chem. 287 (34), 29021–29034. 10.1074/jbc.M112.380147 PubMed DOI PMC

Zahradka J., van Heusden G. P., Sychrova H. (2012). Yeast 14-3-3 proteins participate in the regulation of cell cation homeostasis via interaction with Nha1 alkali-metal-cation/proton antiporter. Biochimica Biophysica Acta 1820 (7), 849–858. 10.1016/j.bbagen.2012.03.013 PubMed DOI

Zhang F., Pracheil T., Thornton J., Liu Z. (2013). Adenosine triphosphate (ATP) is a candidate signaling molecule in the mitochondria-to-nucleus retrograde response pathway. Genes. (Basel) 4 (1), 86–100. 10.3390/genes4010086 PubMed DOI PMC

Zhang L., Winkler S., Schlottmann F. P., Kohlbacher O., Elias J. E., Skotheim J. M., et al. (2019). Multiple layers of phospho-regulation coordinate metabolism and the cell cycle in budding yeast. Front. Cell. Dev. Biol. 7, 338. 10.3389/fcell.2019.00338 PubMed DOI PMC

Zhang R., Feng W., Qian S., Li S., Wang F. (2023). Regulation of Rim4 distribution, function, and stability during meiosis by PKA, Cdc14, and 14-3-3 proteins. Cell. Rep. 42 (9), 113052. 10.1016/j.celrep.2023.113052 PubMed DOI PMC

Zhang Y., Sinning I., Rospert S. (2017). Two chaperones locked in an embrace: structure and function of the ribosome-associated complex RAC. Nat. Struct. Mol. Biol. 24 (8), 611–619. 10.1038/nsmb.3435 PubMed DOI

Zhao G., Chen Y., Carey L., Futcher B. (2016). Cyclin-dependent kinase Co-ordinates carbohydrate metabolism and cell cycle in S. cerevisiae . Mol. Cell. 62 (4), 546–557. 10.1016/j.molcel.2016.04.026 PubMed DOI PMC

Zhou D. R., Eid R., Boucher E., Miller K. A., Mandato C. A., Greenwood M. T. (2019). Stress is an agonist for the induction of programmed cell death: a review. Biochim. Biophys. Acta Mol. Cell. Res. 1866 (4), 699–712. 10.1016/j.bbamcr.2018.12.001 PubMed DOI