Gene Symbol: CNB1
Description: calcineurin regulatory subunit B
Alias: CRV1, YCN2, calcineurin regulatory subunit B
Species: Saccharomyces cerevisiae S288c

Top Publications

  1. Stathopoulos A, Cyert M. Calcineurin acts through the CRZ1/TCN1-encoded transcription factor to regulate gene expression in yeast. Genes Dev. 1997;11:3432-44 pubmed
    ..Thus, in response to multiple signals, calcineurin acts through the Crz1p transcription factor to differentially regulate the expression of several target genes in yeast. ..
  2. Jiang B, Cyert M. Identification of a novel region critical for calcineurin function in vivo and in vitro. J Biol Chem. 1999;274:18543-51 pubmed
  3. Dudgeon D, Zhang N, Ositelu O, Kim H, Cunningham K. Nonapoptotic death of Saccharomyces cerevisiae cells that is stimulated by Hsp90 and inhibited by calcineurin and Cmk2 in response to endoplasmic reticulum stresses. Eukaryot Cell. 2008;7:2037-51 pubmed publisher
    ..These findings reveal a novel prodeath role for Hsp90 and antideath roles for calcineurin and Cmk2 that extend the life span of S. cerevisiae cells responding to both natural and clinical antifungal compounds. ..
  4. Zhao C, Jung U, Garrett Engele P, Roe T, Cyert M, Levin D. Temperature-induced expression of yeast FKS2 is under the dual control of protein kinase C and calcineurin. Mol Cell Biol. 1998;18:1013-22 pubmed
    ..Therefore, a double mutant in calcineurin (CNB1) and FKS1 is inviable due to a deficiency in FKS2 expression...
  5. Gururaj C, Federman R, Federman R, Chang A. Orm proteins integrate multiple signals to maintain sphingolipid homeostasis. J Biol Chem. 2013;288:20453-63 pubmed publisher
    ..Conversely, the calcium- and calcineurin-dependent pathway signals ER stress response upon lipid dysregulation in the absence of the Orm proteins to restore ER homeostasis. ..
  6. Noma S, Iida K, Iida H. Polarized morphogenesis regulator Spa2 is required for the function of putative stretch-activated Ca2+-permeable channel component Mid1 in Saccharomyces cerevisiae. Eukaryot Cell. 2005;4:1353-63 pubmed
    ..Therefore, we suggest that Mid1 function is influenced by Spa2 function through polarized morphogenesis. ..
  7. Erez O, Kahana C. Screening for modulators of spermine tolerance identifies Sky1, the SR protein kinase of Saccharomyces cerevisiae, as a regulator of polyamine transport and ion homeostasis. Mol Cell Biol. 2001;21:175-84 pubmed
    ..While deletion or overexpression of SKY1 did not significantly affect Pma1p activity, the ability of overexpressed Sky1p, Ptk1p, and Ptk2p to increase sensitivity to LiCl depends on the integrity of PPZ1 but not of ENA1. ..
  8. Rios G, Ferrando A, Serrano R. Mechanisms of salt tolerance conferred by overexpression of the HAL1 gene in Saccharomyces cerevisiae. Yeast. 1997;13:515-28 pubmed
    ..As a consequence, osmotic adjustment through glycerolsynthesis, a process not affected by HAL1, is the limiting factor for growth on galactose under NaCl stressed. ..
  9. Chen S, Tarsio M, Kane P, Greenberg M. Cardiolipin mediates cross-talk between mitochondria and the vacuole. Mol Biol Cell. 2008;19:5047-58 pubmed publisher
    ..Our results demonstrate the existence of a novel mitochondria-vacuole signaling pathway mediated by CL synthesis. ..

More Information


  1. Shitamukai A, Hirata D, Sonobe S, Miyakawa T. Evidence for antagonistic regulation of cell growth by the calcineurin and high osmolarity glycerol pathways in Saccharomyces cerevisiae. J Biol Chem. 2004;279:3651-61 pubmed
    ..redundant function(s) in the events essential for growth, the simultaneous deletion of both these pathways (Delta cnb1 Delta mpk1) leads to lethality...
  2. Parent S, Nielsen J, Morin N, Chrebet G, Ramadan N, Dahl A, et al. Calcineurin-dependent growth of an FK506- and CsA-hypersensitive mutant of Saccharomyces cerevisiae. J Gen Microbiol. 1993;139:2973-84 pubmed
    ..two genes (CNA1 and CNA2) encoding the alternative forms of the catalytic A subunit of calcineurin, or of the gene (CNB1) encoding the regulatory B subunit, is lethal in an fks1 mutant...
  3. Tsubakiyama R, Mizunuma M, Gengyo A, Yamamoto J, Kume K, Miyakawa T, et al. Implication of Ca2+ in the regulation of replicative life span of budding yeast. J Biol Chem. 2011;286:28681-7 pubmed publisher
    ..Thus, our results indicate that Ca(2+) homeostasis/Ca(2+) signaling are required to regulate longevity in budding yeast. ..
  4. Hemenway C, Heitman J. Lic4, a nuclear phosphoprotein that cooperates with calcineurin to regulate cation homeostasis in Saccharomyces cerevisiae. Mol Gen Genet. 1999;261:388-401 pubmed
    ..Taken together, our findings support a model in which calcineurin and Lic4 are components of signalling cascades that regulate cation stress responses in yeast. ..
  5. Gardarin A, Chédin S, Lagniel G, Aude J, Godat E, Catty P, et al. Endoplasmic reticulum is a major target of cadmium toxicity in yeast. Mol Microbiol. 2010;76:1034-48 pubmed publisher
    ..In particular, Cd(2+) activates the calcium channel Cch1/Mid1, which also contributes to Cd(2+) entry into the cell. The results reinforce the interest of using yeast as a cellular model to study toxicity mechanisms in eukaryotic cells. ..
  6. Mizunuma M, Hirata D, Miyaoka R, Miyakawa T. GSK-3 kinase Mck1 and calcineurin coordinately mediate Hsl1 down-regulation by Ca2+ in budding yeast. EMBO J. 2001;20:1074-85 pubmed
    ..The Ca2+-activated pathway may play a role in the rapid inactivation of Hsl1 at the cell cycle stage(s) when APC activity is low. ..
  7. Marquina M, González A, Barreto L, Gelis S, Munoz I, Ruiz A, et al. Modulation of yeast alkaline cation tolerance by Ypi1 requires calcineurin. Genetics. 2012;190:1355-64 pubmed publisher
    ..Deletion of CNB1, encoding the regulatory subunit of the calcineurin phosphatase, blocked Ypi1-induced expression of ENA1, ..
  8. Ferreira R, Silva A, Pimentel C, Batista Nascimento L, Rodrigues Pousada C, Menezes R. Arsenic stress elicits cytosolic Ca(2+) bursts and Crz1 activation in Saccharomyces cerevisiae. Microbiology. 2012;158:2293-302 pubmed publisher
    ..and translocated to the nucleus, and stimulates CDRE-driven expression of the lacZ reporter gene in a Cnb1-dependent manner...
  9. Alepuz P, Matheos D, Cunningham K, Estruch F. The Saccharomyces cerevisiae RanGTP-binding protein msn5p is involved in different signal transduction pathways. Genetics. 1999;153:1219-31 pubmed
    ..Therefore, Msn5p could be a receptor for several proteins involved in different signaling pathways. ..
  10. Cagnac O, Aranda Sicilia M, Leterrier M, Rodriguez Rosales M, Venema K. Vacuolar cation/H+ antiporters of Saccharomyces cerevisiae. J Biol Chem. 2010;285:33914-22 pubmed publisher
    ..The relative importance of Nhx1p, Vnx1p, and Vcx1p in the vacuolar accumulation of monovalent cations will be discussed. ..
  11. Mendoza I, Quintero F, Bressan R, Hasegawa P, Pardo J. Activated calcineurin confers high tolerance to ion stress and alters the budding pattern and cell morphology of yeast cells. J Biol Chem. 1996;271:23061-7 pubmed
    ..These results suggest that calcineurin may also act in the establishment of cell polarity. ..
  12. Kume K, Koyano T, Takata J, Wakabayashi K, Mizunuma M, Miyakawa T, et al. Screening for a gene deletion mutant whose temperature sensitivity is suppressed by FK506 in budding yeast and its application for a positive screening for drugs inhibiting calcineurin. Biosci Biotechnol Biochem. 2015;79:790-4 pubmed publisher
    ..been deleted, which gene is required for actin organization and endocytosis, was suppressed by either FK506 or by cnb1 deletion. Indeed, the calcineurin activity increased significantly in the ∆vrp1 cells...
  13. Casado C, Yenush L, Melero C, Ruiz M, Serrano R, Perez Valle J, et al. Regulation of Trk-dependent potassium transport by the calcineurin pathway involves the Hal5 kinase. FEBS Lett. 2010;584:2415-20 pubmed publisher
    ..However, the growth defect of cnb1 cells at K(+)-limiting conditions can be rescued in part by overexpression of HAL5, and this mutation further ..
  14. Rodriguez A, Roy J, Martínez Martínez S, López Maderuelo M, Niño Moreno P, Ortí L, et al. A conserved docking surface on calcineurin mediates interaction with substrates and immunosuppressants. Mol Cell. 2009;33:616-26 pubmed publisher
    ..These studies suggest that LxVP-type sites are a common feature of calcineurin substrates, and that immunosuppressant-immunophilin complexes inhibit calcineurin by interfering with this mode of substrate recognition. ..
  15. Roy J, Li H, Hogan P, Cyert M. A conserved docking site modulates substrate affinity for calcineurin, signaling output, and in vivo function. Mol Cell. 2007;25:889-901 pubmed
    ..Thus, calcineurin-substrate affinity determines the Ca(2+) concentration dependence and output of signaling in vivo as well as the balance between different branches of calcineurin signaling in an overall biological response. ..
  16. Vlahakis A, Graef M, Nunnari J, Powers T. TOR complex 2-Ypk1 signaling is an essential positive regulator of the general amino acid control response and autophagy. Proc Natl Acad Sci U S A. 2014;111:10586-91 pubmed publisher
    ..Our work reveals that the TORC2 pathway regulates autophagy in an opposing manner to TORC1 to provide a tunable response to cellular metabolic status. ..
  17. Zhao Y, Xu H, Zhang Y, Jiang L. Vcx1-D1 (M383I), the Vcx1 mutant with a calcineurin-independent vacuolar Ca(2+)/H(+) exchanger activity, confers calcineurin-independent Mn(2+) tolerance in Saccharomyces cerevisiae. Can J Microbiol. 2016;62:475-84 pubmed publisher
  18. Kobayashi Y, Inai T, Mizunuma M, Okada I, Shitamukai A, Hirata D, et al. Identification of Tup1 and Cyc8 mutations defective in the responses to osmotic stress. Biochem Biophys Res Commun. 2008;368:50-5 pubmed publisher
  19. Tanida I, Hasegawa A, Iida H, Ohya Y, Anraku Y. Cooperation of calcineurin and vacuolar H(+)-ATPase in intracellular Ca2+ homeostasis of yeast cells. J Biol Chem. 1995;270:10113-9 pubmed
    ..their binding proteins and ascribable to inhibition of calcineurin activity; a mutation of a calcineurin subunit (cnb1) shows synthetic lethal interaction with the vma mutation...
  20. Nakamura T, Ohmoto T, Hirata D, Tsuchiya E, Miyakawa T. Genetic evidence for the functional redundancy of the calcineurin- and Mpk1-mediated pathways in the regulation of cellular events important for growth in Saccharomyces cerevisiae. Mol Gen Genet. 1996;251:211-9 pubmed
    ..The mutants were classified into four complementation groups (crv1,2,3 and 4). Crv1 was allelic to cnb1, a mutation in the regulatory subunit of calcineurin...
  21. Tabuchi M, Audhya A, Parsons A, Boone C, Emr S. The phosphatidylinositol 4,5-biphosphate and TORC2 binding proteins Slm1 and Slm2 function in sphingolipid regulation. Mol Cell Biol. 2006;26:5861-75 pubmed
    ..Together, our data suggest that Slm1 and Slm2 define a molecular link between phosphoinositide and sphingolipid signaling and thereby regulate actin cytoskeleton organization. ..
  22. Mulet J, Martin D, Loewith R, Hall M. Mutual antagonism of target of rapamycin and calcineurin signaling. J Biol Chem. 2006;281:33000-7 pubmed
    ..Thus, TORC2-SLM signaling negatively regulates calcineurin, and calcineurin negatively regulates TORC2-SLM. These findings provide a molecular basis for the mutual antagonism of growth and stress. ..
  23. Aronova S, Wedaman K, Aronov P, Fontes K, Ramos K, Hammock B, et al. Regulation of ceramide biosynthesis by TOR complex 2. Cell Metab. 2008;7:148-58 pubmed publisher
    ..Because Ypk2 is activated independently by LCBs, the direct precursors to ceramides, our data suggest a model wherein TORC2 signaling is coupled with LCB levels to control Ypk2 activity and, ultimately, regulate ceramide formation. ..
  24. Ruiz A, González A, García Salcedo R, Ramos J, Arino J. Role of protein phosphatases 2C on tolerance to lithium toxicity in the yeast Saccharomyces cerevisiae. Mol Microbiol. 2006;62:263-77 pubmed
    ..These results indicate that Ptc1p modulates the function of Ena1p by regulating the Hal3/Ppz1,2 pathway. In conclusion, overexpression of PTC3 and lack of PTC1 affect lithium tolerance in yeast, although through different mechanisms. ..
  25. Kingsbury T, Cunningham K. A conserved family of calcineurin regulators. Genes Dev. 2000;14:1595-604 pubmed
  26. Ganster R, McCartney R, Schmidt M. Identification of a calcineurin-independent pathway required for sodium ion stress response in Saccharomyces cerevisiae. Genetics. 1998;150:31-42 pubmed
    ..Taken together, our data demonstrate that response to ion stress requires the participation of both calcineurin-dependent and -independent pathways. ..
  27. Mizunuma M, Hirata D, Miyahara K, Tsuchiya E, Miyakawa T. Role of calcineurin and Mpk1 in regulating the onset of mitosis in budding yeast. Nature. 1998;392:303-6 pubmed
    ..These cellular pathways also induce a G2-phase delay in response to hypotonic shock. ..
  28. Laviña W, Hermansyah -, Sugiyama M, Kaneko Y, Harashima S. Functionally redundant protein phosphatase genes PTP2 and MSG5 co-regulate the calcium signaling pathway in Saccharomyces cerevisiae upon exposure to high extracellular calcium concentration. J Biosci Bioeng. 2013;115:138-46 pubmed publisher
    ..this paper, we found that the inactivation of calcineurin by the disruption of the calcineurin regulatory subunit, CNB1 or treatment with a calcineurin inhibitor, FK506, can suppress the calcium-sensitive phenotype of the ptp2?msg5? ..
  29. Rusnak F, Mertz P. Calcineurin: form and function. Physiol Rev. 2000;80:1483-521 pubmed
    ..This review provides a comprehensive examination of the biological roles of calcineurin and reviews aspects related to its structure and catalytic mechanism...
  30. Uesugi S, Watanabe D, Kitajima M, Watanabe R, Kawamura Y, Ohnishi M, et al. Calcineurin inhibitors suppress the high-temperature stress sensitivity of the yeast ubiquitin ligase Rsp5 mutant: a new method of screening for calcineurin inhibitors. FEMS Yeast Res. 2014;14:567-74 pubmed
    ..The defect of calcineurin pathway by disrupting the CNB1 and CRZ1 gene also partially complemented the high-temperature stress sensitivity of rsp5(A401E) cells...
  31. Withee J, Sen R, Cyert M. Ion tolerance of Saccharomyces cerevisiae lacking the Ca2+/CaM-dependent phosphatase (calcineurin) is improved by mutations in URE2 or PMA1. Genetics. 1998;149:865-78 pubmed
    ..These studies further characterize the roles that URE2 and PMA1 play in regulating intracellular ion homeostasis. ..
  32. Zhao Y, Du J, Xiong B, Xu H, Jiang L. ESCRT components regulate the expression of the ER/Golgi calcium pump gene PMR1 through the Rim101/Nrg1 pathway in budding yeast. J Mol Cell Biol. 2013;5:336-44 pubmed publisher
    ..Collectively, these data have uncovered a function of ESCRT components in regulating PMR1 expression through the Nrg1/Rim101 pathway. Our findings provide important clues for understanding human diseases related to calcium homeostasis. ..
  33. Eng W, Faucette L, McLaughlin M, Cafferkey R, Koltin Y, Morris R, et al. The yeast FKS1 gene encodes a novel membrane protein, mutations in which confer FK506 and cyclosporin A hypersensitivity and calcineurin-dependent growth. Gene. 1994;151:61-71 pubmed
    ..These data suggest that FKS1 provides a unique cellular function which, when absent, increases FK506 and CsA sensitivity by making the CNs (or a CN-dependent function) essential. ..
  34. Cyert M, Thorner J. Regulatory subunit (CNB1 gene product) of yeast Ca2+/calmodulin-dependent phosphoprotein phosphatases is required for adaptation to pheromone. Mol Cell Biol. 1992;12:3460-9 pubmed
    ..These antibodies were used to isolate the structural gene (CNB1) encoding this protein from a yeast expression library in the vector lambda gt11...
  35. Niles B, Mogri H, Hill A, Vlahakis A, Powers T. Plasma membrane recruitment and activation of the AGC kinase Ypk1 is mediated by target of rapamycin complex 2 (TORC2) and its effector proteins Slm1 and Slm2. Proc Natl Acad Sci U S A. 2012;109:1536-41 pubmed publisher
    ..These findings both extend the scope of cellular processes regulated by Ypk1/2 to include negative regulation of calcineurin and broaden the repertoire of mechanisms for membrane recruitment and activation of a protein kinase. ..
  36. Wang X, Sheff M, Simpson D, Elion E. Ste11p MEKK signals through HOG, mating, calcineurin and PKC pathways to regulate the FKS2 gene. BMC Mol Biol. 2011;12:51 pubmed publisher
    ..The patterns of control by Ste11p targets revealed novel functional linkages, cross-regulation, redundancy and compensation. ..
  37. Ferrer Dalmau J, González A, Platara M, Navarrete C, Martinez J, Barreto L, et al. Ref2, a regulatory subunit of the yeast protein phosphatase 1, is a novel component of cation homoeostasis. Biochem J. 2010;426:355-64 pubmed publisher
    ..Remarkably, the evidence collected indicates that the role of Ref2 in cation homoeostasis may be unrelated to its previously identified function in the formation of mRNA via the APT (for associated with Pta1) complex. ..