Gene Symbol: TEM1
Description: Ras family GTPase TEM1
Alias: Ras family GTPase TEM1
Species: Saccharomyces cerevisiae S288c
Products:     TEM1

Top Publications

  1. Shirayama M, Matsui Y, Toh e A. The yeast TEM1 gene, which encodes a GTP-binding protein, is involved in termination of M phase. Mol Cell Biol. 1994;14:7476-82 pubmed
    ..Previously we have shown that LTE1 is essential for termination of M phase at low temperatures. We have identified TEM1 as a gene that, when present on a multicopy plasmid, suppresses the cold-sensitive phenotype of lte1...
  2. Ro H, Song S, Lee K. Bfa1 can regulate Tem1 function independently of Bub2 in the mitotic exit network of Saccharomyces cerevisiae. Proc Natl Acad Sci U S A. 2002;99:5436-41 pubmed
    ..Although it is not clear at present how mitotic exit is triggered, a growing body of evidence suggests that the Tem1 GTPase plays a critical role in mediating this pathway and that Bfa1 and Bub2 constitute a two-component GTPase-..
  3. Visintin R, Amon A. Regulation of the mitotic exit protein kinases Cdc15 and Dbf2. Mol Biol Cell. 2001;12:2961-74 pubmed
    ..It is comprised of the RAS-like GTP binding protein Tem1, the exchange factor Lte1, the GTPase activating protein complex Bub2-Bfa1/Byr4, and several protein kinases ..
  4. Kim J, Jang S, Song K. Different levels of Bfa1/Bub2 GAP activity are required to prevent mitotic exit of budding yeast depending on the type of perturbations. Mol Biol Cell. 2008;19:4328-40 pubmed publisher
    In budding yeast, Tem1 is a key regulator of mitotic exit. Bfa1/Bub2 stimulates Tem1 GTPase activity as a GTPase-activating protein (GAP). Lte1 possesses a guanine-nucleotide exchange factor (GEF) domain likely for Tem1...
  5. Wang Y, Shirogane T, Liu D, Harper J, Elledge S. Exit from exit: resetting the cell cycle through Amn1 inhibition of G protein signaling. Cell. 2003;112:697-709 pubmed
    In S. cerevisiae cells undergoing anaphase, a ras-related GTPase, Tem1, is located on the spindle pole body that enters the daughter cell and activates a signal transduction pathway, MEN, to allow mitotic exit...
  6. Lippincott J, Shannon K, Shou W, Deshaies R, Li R. The Tem1 small GTPase controls actomyosin and septin dynamics during cytokinesis. J Cell Sci. 2001;114:1379-86 pubmed
    ..Because the Tem1 small GTPase (Tem1p) is required for the completion of mitosis, we investigated its role in regulating septin and ..
  7. Monje Casas F, Amon A. Cell polarity determinants establish asymmetry in MEN signaling. Dev Cell. 2009;16:132-45 pubmed publisher
    ..Our results indicate that mother-daughter cell asymmetry determinants establish MEN signaling asymmetry through microtubule-bud cortex interactions. ..
  8. Corbett M, Xiong Y, Boyne J, Wright D, Munro E, Price C. IQGAP and mitotic exit network (MEN) proteins are required for cytokinesis and re-polarization of the actin cytoskeleton in the budding yeast, Saccharomyces cerevisiae. Eur J Cell Biol. 2006;85:1201-15 pubmed
    ..These data establish a mechanistic dependency of cell separation upon an intermediate step requiring actomyosin ring assembly. ..
  9. Bardin A, Boselli M, Amon A. Mitotic exit regulation through distinct domains within the protein kinase Cdc15. Mol Cell Biol. 2003;23:5018-30 pubmed
    ..Our findings indicate that multiple modes of MEN regulation occur through the protein kinase Cdc15. ..

More Information


  1. Meitinger F, Petrova B, Lombardi I, Bertazzi D, Hub B, Zentgraf H, et al. Targeted localization of Inn1, Cyk3 and Chs2 by the mitotic-exit network regulates cytokinesis in budding yeast. J Cell Sci. 2010;123:1851-61 pubmed publisher
    ..This defect was partially suppressed by increased levels of Cyk3. We therefore propose that the MEN directly controls cytokinesis via targeting of Inn1, Cyk3 and Chs2 to the bud neck...
  2. Zhao X, Chang A, Toh e A, Arvan P. A role for Lte1p (a low temperature essential protein involved in mitosis) in proprotein processing in the yeast secretory pathway. J Biol Chem. 2007;282:1670-8 pubmed
    ..By sequence analysis, Tem1p has highest similarity to Vps21p (yeast homolog of mammalian Rab5). Unlike TEM1, LTE1 is not restricted to mitosis but is expressed throughout the cell cycle...
  3. Fraschini R, D Ambrosio C, Venturetti M, Lucchini G, Piatti S. Disappearance of the budding yeast Bub2-Bfa1 complex from the mother-bound spindle pole contributes to mitotic exit. J Cell Biol. 2006;172:335-46 pubmed
    ..position checkpoint is engaged by misoriented spindles and prevents mitotic exit by inhibiting the G protein Tem1 through the GTPase-activating protein (GAP) Bub2/Bfa1...
  4. D Aquino K, Monje Casas F, Paulson J, Reiser V, Charles G, Lai L, et al. The protein kinase Kin4 inhibits exit from mitosis in response to spindle position defects. Mol Cell. 2005;19:223-34 pubmed
  5. Visintin R, Stegmeier F, Amon A. The role of the polo kinase Cdc5 in controlling Cdc14 localization. Mol Biol Cell. 2003;14:4486-98 pubmed
    ..Cdc5 promotes Cdc14 phosphorylation and, by stimulating the MEN, Cfi1/Net1 phosphorylation. Furthermore, we suggest that Cdc14 release from the nucleolus only occurs when Cdc14 and Cfi1/Net1 are both phosphorylated. ..
  6. Morishita T, Mitsuzawa H, Nakafuku M, Nakamura S, Hattori S, Anraku Y. Requirement of Saccharomyces cerevisiae Ras for completion of mitosis. Science. 1995;270:1213-5 pubmed
    ..The lethality of the triple disruption was suppressed by the multicopies of CDC5, CDC15, DBF2, SPO12, and TEM1, all of which function in the completion of the M phase...
  7. Tinker Kulberg R, Morgan D. Pds1 and Esp1 control both anaphase and mitotic exit in normal cells and after DNA damage. Genes Dev. 1999;13:1936-49 pubmed
    ..are dependent on Cdc20 (an activating subunit of the APC) and on several additional proteins (Cdc5, Cdc14, Cdc15, Tem1) that form a regulatory network governing mitotic exit...
  8. Jaspersen S, Morgan D. Cdc14 activates cdc15 to promote mitotic exit in budding yeast. Curr Biol. 2000;10:615-8 pubmed
    ..Instead, Cdc15 dephosphorylation may promote some additional function of Cdc15 that is independent of its effects on Cdc14 activation. ..
  9. Lee S, Jensen S, Frenz L, Johnson A, Fesquet D, Johnston L. The Bub2-dependent mitotic pathway in yeast acts every cell cycle and regulates cytokinesis. J Cell Sci. 2001;114:2345-54 pubmed
    ..This cell-cycle arrest depends upon inhibition of the G-protein Tem1 that appears to be regulated by Bfa1/Bub2, a two-component GTPase-activating protein, and the exchange factor Lte1...
  10. Shou W, Seol J, Baskerville C, Moazed D, Chen Z, Jang J, et al. Exit from mitosis is triggered by Tem1-dependent release of the protein phosphatase Cdc14 from nucleolar RENT complex. Cell. 1999;97:233-44 pubmed
    Exit from mitosis in budding yeast requires a group of essential proteins--including the GTPase Tem1 and the protein phosphatase Cdc14--that downregulate cyclin-dependent kinase activity...
  11. Geymonat M, Spanos A, de Bettignies G, Sedgwick S. Lte1 contributes to Bfa1 localization rather than stimulating nucleotide exchange by Tem1. J Cell Biol. 2009;187:497-511 pubmed publisher
    Lte1 is a mitotic regulator long envisaged as a guanosine nucleotide exchange factor (GEF) for Tem1, the small guanosine triphosphatase governing activity of the Saccharomyces cerevisiae mitotic exit network...
  12. Rahal R, Amon A. The Polo-like kinase Cdc5 interacts with FEAR network components and Cdc14. Cell Cycle. 2008;7:3262-72 pubmed
    ..Finally, we present evidence that the Cdc5-Cdc14 association is direct, further supporting the central role of Cdc5 in Cdc14 localization. ..
  13. Pereira G, Höfken T, Grindlay J, Manson C, Schiebel E. The Bub2p spindle checkpoint links nuclear migration with mitotic exit. Mol Cell. 2000;6:1-10 pubmed
    ..Since components of the Bub2p checkpoint are conserved in other organisms, we propose that the position of the SPB or mammalian centrosome controls the timing of mitotic exit. ..
  14. Geymonat M, Spanos A, Smith S, Wheatley E, Rittinger K, Johnston L, et al. Control of mitotic exit in budding yeast. In vitro regulation of Tem1 GTPase by Bub2 and Bfa1. J Biol Chem. 2002;277:28439-45 pubmed
    ..Extensive genetic data indicate that mitotic exit network activity is determined by a GTP-binding protein, Tem1, and its putative regulators, Bub2, Bfa1, and Lte1...
  15. Höfken T, Schiebel E. A role for cell polarity proteins in mitotic exit. EMBO J. 2002;21:4851-62 pubmed
    ..The G protein Tem1 regulates MEN activity...
  16. Gruneberg U, Campbell K, Simpson C, Grindlay J, Schiebel E. Nud1p links astral microtubule organization and the control of exit from mitosis. EMBO J. 2000;19:6475-88 pubmed
    ..Thus, in nud1-2 cells the failure of Tem1p to interact with Cdc15p at the SPB probably prevents mitotic exit. ..
  17. Valerio Santiago M, Monje Casas F. Tem1 localization to the spindle pole bodies is essential for mitotic exit and impairs spindle checkpoint function. J Cell Biol. 2011;192:599-614 pubmed publisher
    ..The GTPase Tem1 localizes on the spindle pole bodies (SPBs) and initiates MEN signaling...
  18. Kim J, Jeong J, Song K. The C-terminus of Bfa1p in budding yeast is essential to induce mitotic arrest in response to diverse checkpoint-activating signals. Genes Cells. 2004;9:399-418 pubmed
  19. Fraschini R, Bilotta D, Lucchini G, Piatti S. Functional characterization of Dma1 and Dma2, the budding yeast homologues of Schizosaccharomyces pombe Dma1 and human Chfr. Mol Biol Cell. 2004;15:3796-810 pubmed
    ..In case of altered spindle orientation, the spindle position checkpoint inhibits Tem1-dependent activation of the mitotic exit network (MEN), thus delaying mitotic exit and cytokinesis until errors are ..
  20. Asakawa K, Yoshida S, Otake F, Toh e A. A novel functional domain of Cdc15 kinase is required for its interaction with Tem1 GTPase in Saccharomyces cerevisiae. Genetics. 2001;157:1437-50 pubmed
    ..By the two-hybrid screening, we identified Cdc15 as a binding protein of Tem1 GTPase, another essential regulator of the MEN...
  21. Visintin R, Craig K, Hwang E, Prinz S, Tyers M, Amon A. The phosphatase Cdc14 triggers mitotic exit by reversal of Cdk-dependent phosphorylation. Mol Cell. 1998;2:709-18 pubmed
    ..Feedback between these pathways may lead to precipitous collapse of mitotic CDK activity and help coordinate exit from mitosis. ..
  22. Bardin A, Visintin R, Amon A. A mechanism for coupling exit from mitosis to partitioning of the nucleus. Cell. 2000;102:21-31 pubmed
    ..We find that the GTP binding protein Tem1, a regulator of mitotic exit, is present on the spindle pole body that migrates into the bud during S phase and ..
  23. Shou W, Sakamoto K, Keener J, Morimoto K, Traverso E, Azzam R, et al. Net1 stimulates RNA polymerase I transcription and regulates nucleolar structure independently of controlling mitotic exit. Mol Cell. 2001;8:45-55 pubmed
    ..The independent functions of Net1 link a key event in the cell cycle to nucleolar processes that are fundamental to cell growth. ..
  24. Shannon K, Li R. The multiple roles of Cyk1p in the assembly and function of the actomyosin ring in budding yeast. Mol Biol Cell. 1999;10:283-96 pubmed
    ..These results demonstrate the critical function of Cyk1p/Iqg1p in regulating various steps of actomyosin ring assembly and cytokinesis. ..
  25. Hu F, Wang Y, Liu D, Li Y, Qin J, Elledge S. Regulation of the Bub2/Bfa1 GAP complex by Cdc5 and cell cycle checkpoints. Cell. 2001;107:655-65 pubmed
    During mitosis, a ras-related GTPase (Tem1) binds GTP and activates a signal transduction pathway to allow mitotic exit. During most of the cell cycle, Tem1 function is antagonized by a GTPase-activating protein complex, Bfa1/Bub2...
  26. Jaspersen S, Charles J, Tinker Kulberg R, Morgan D. A late mitotic regulatory network controlling cyclin destruction in Saccharomyces cerevisiae. Mol Biol Cell. 1998;9:2803-17 pubmed
    ..Saccharomyces cerevisiae, members of a large class of late mitotic mutants, including cdc15, cdc5, cdc14, dbf2, and tem1, arrest in anaphase with a phenotype similar to that of cells expressing nondegradable forms of mitotic cyclins...
  27. Pereira G, Manson C, Grindlay J, Schiebel E. Regulation of the Bfa1p-Bub2p complex at spindle pole bodies by the cell cycle phosphatase Cdc14p. J Cell Biol. 2002;157:367-79 pubmed
    ..These data indicate that Cdc14p activates the MEN in early anaphase but later inactivates it through Bfa1p dephosphorylation and so restricts MEN activity to a short period in anaphase. ..
  28. Visintin R, Hwang E, Amon A. Cfi1 prevents premature exit from mitosis by anchoring Cdc14 phosphatase in the nucleolus. Nature. 1999;398:818-23 pubmed
    ..A highly conserved signalling cascade, critical for the exit from mitosis, is required for this movement of Cdc14 during anaphase. Furthermore, we have identified a negative regulator of Cdc14, Cfi1, that anchors Cdc14 in the nucleolus. ..
  29. Höfken T, Schiebel E. Novel regulation of mitotic exit by the Cdc42 effectors Gic1 and Gic2. J Cell Biol. 2004;164:219-31 pubmed
    ..Moreover, Gic1 bound directly to Bub2 and prevented binding of the GTPase Tem1 to Bub2...
  30. Hotz M, Leisner C, Chen D, Manatschal C, Wegleiter T, Ouellet J, et al. Spindle pole bodies exploit the mitotic exit network in metaphase to drive their age-dependent segregation. Cell. 2012;148:958-72 pubmed publisher
    ..We propose that MEN signaling links Kar9 regulation to SPB identity through biasing and stabilizing the age-insensitive, cyclin-B-dependent mechanism of symmetry breaking. ..
  31. Kim J, Luo G, Bahk Y, Song K. Cdc5-dependent asymmetric localization of bfa1 fine-tunes timely mitotic exit. PLoS Genet. 2012;8:e1002450 pubmed publisher
    In budding yeast, the major regulator of the mitotic exit network (MEN) is Tem1, a GTPase, which is inhibited by the GTPase-activating protein (GAP), Bfa1/Bub2...
  32. Cassani C, Raspelli E, Santo N, Chiroli E, Lucchini G, Fraschini R. Saccharomyces cerevisiae Dma proteins participate in cytokinesis by controlling two different pathways. Cell Cycle. 2013;12:2794-808 pubmed publisher
    ..In addition, overproduction of Dma2 impairs the interaction between Tem1 and Iqg1, which is thought to be required for AMR contraction, and causes asymmetric primary septum deposition as ..
  33. Asakawa K, Toh e A. A defect of Kap104 alleviates the requirement of mitotic exit network gene functions in Saccharomyces cerevisiae. Genetics. 2002;162:1545-56 pubmed
    ..These results suggest that a mutation in Kap104 stimulates exit from mitosis through the activation of Cdc14 and implies a novel role for Kap104 in cell-cycle progression in budding yeast. ..
  34. Rossio V, Galati E, Ferrari M, Pellicioli A, Sutani T, Shirahige K, et al. The RSC chromatin-remodeling complex influences mitotic exit and adaptation to the spindle assembly checkpoint by controlling the Cdc14 phosphatase. J Cell Biol. 2010;191:981-97 pubmed publisher
    ..Our data suggest that fine-tuning regulators of mitotic exit have important functions during mitotic progression in cells treated with microtubule poisons and might be promising targets for cancer treatment. ..
  35. Li J, Wang L, Wu X, Fang O, Wang L, Lu C, et al. Polygenic molecular architecture underlying non-sexual cell aggregation in budding yeast. DNA Res. 2013;20:55-66 pubmed publisher
  36. Scarfone I, Venturetti M, Hotz M, Lengefeld J, Barral Y, Piatti S. Asymmetry of the budding yeast Tem1 GTPase at spindle poles is required for spindle positioning but not for mitotic exit. PLoS Genet. 2015;11:e1004938 pubmed publisher
    ..SPOC relies on the heterodimeric GTPase-activating protein Bub2/Bfa1 that inhibits the small GTPase Tem1, in turn essential for activating the mitotic exit network (MEN) kinase cascade and cytokinesis...
  37. Wang Y, Ng T. Phosphatase 2A negatively regulates mitotic exit in Saccharomyces cerevisiae. Mol Biol Cell. 2006;17:80-9 pubmed
    ..All the evidence suggests the negative role of PP2A in mitotic exit. Finally, our genetic and biochemical data suggest that PP2A regulates the phosphorylation of Tem1, which acts at the very top of MEN pathway.
  38. Scarfone I, Piatti S. Coupling spindle position with mitotic exit in budding yeast: The multifaceted role of the small GTPase Tem1. Small Gtpases. 2015;6:196-201 pubmed publisher
    ..The small GTPase Tem1 is required to trigger a Hippo-like protein kinase cascade, named Mitotic Exit Network (MEN), that is essential for ..
  39. Grandin N, de Almeida A, Charbonneau M. The Cdc14 phosphatase is functionally associated with the Dbf2 protein kinase in Saccharomyces cerevisiae. Mol Gen Genet. 1998;258:104-16 pubmed
    ..2 M sorbitol to the culture medium. Our data are the first to demonstrate a functional link between Cdc14 and Dbf2 based on both biochemical and genetic information. ..
  40. Shou W, Deshaies R. Multiple telophase arrest bypassed (tab) mutants alleviate the essential requirement for Cdc15 in exit from mitosis in S. cerevisiae. BMC Genet. 2002;3:4 pubmed
    ..Transport-defective mutations in two karyopherins can bypass cdc15Delta, suggesting that the function of the MEN is to promote mitotic exit by regulating nuclear transport. ..
  41. Yellman C, Roeder G. Cdc14 Early Anaphase Release, FEAR, Is Limited to the Nucleus and Dispensable for Efficient Mitotic Exit. PLoS ONE. 2015;10:e0128604 pubmed publisher
    ..Our findings clarify the distinction between FEAR and MEN-dependent Cdc14 activities and will help guide emerging quantitative models of this cell cycle transition. ..
  42. Mancini Lombardi I, Palani S, Meitinger F, Darieva Z, Hofmann A, Sharrocks A, et al. Lre1 directly inhibits the NDR/Lats kinase Cbk1 at the cell division site in a phosphorylation-dependent manner. Curr Biol. 2013;23:1736-45 pubmed publisher
    ..We propose that similar inhibitory proteins may also provide fine tuning for the activity of NDR kinases in other organisms. ..
  43. Krishnan R, Pangilinan F, Lee C, Spencer F. Saccharomyces cerevisiae BUB2 prevents mitotic exit in response to both spindle and kinetochore damage. Genetics. 2000;156:489-500 pubmed
    ..chromatid separation in nocodazole-treated bub2 cells is prevented when mitotic exit is blocked using a conditional tem1(c) mutant, indicating that the preanaphase failure in bub2 cells is a consequence of events downstream of TEM1 in ..
  44. Chan L, Amon A. The protein phosphatase 2A functions in the spindle position checkpoint by regulating the checkpoint kinase Kin4. Genes Dev. 2009;23:1639-49 pubmed publisher
  45. Kim J, Song K. The study of Bfa1p(E438K) suggests that Bfa1 control the mitotic exit network in different mechanisms depending on different checkpoint-activating signals. Mol Cells. 2006;21:251-60 pubmed
    ..In addition, the viability of cdc5-2 delta bfa1 cells was not reduced by BFA1(E438K), suggesting that Cdc5p also regulates Bfa1p to activate mitotic exit by other mechanism(s), besides phosphorylation. ..
  46. Cenamor R, Jimenez J, Cid V, Nombela C, Sanchez M. The budding yeast Cdc15 localizes to the spindle pole body in a cell-cycle-dependent manner. Mol Cell Biol Res Commun. 1999;2:178-84 pubmed
    ..cerevisiae cell cycle is regulated by a regulatory network that involves, among other proteins, the small GTPase Tem1, the protein phosphatase Cdc14, and the protein kinases Dbf2 and Cdc15...
  47. Makanae K, Kintaka R, Makino T, Kitano H, Moriya H. Identification of dosage-sensitive genes in Saccharomyces cerevisiae using the genetic tug-of-war method. Genome Res. 2013;23:300-11 pubmed publisher
    ..The results obtained in this study will provide basic knowledge about the physiology of chromosomal abnormalities and the evolution of chromosomal composition. ..
  48. Makhnevych T, Wong P, Pogoutse O, Vizeacoumar F, Greenblatt J, Emili A, et al. Hsp110 is required for spindle length control. J Cell Biol. 2012;198:623-36 pubmed publisher
    ..These data suggest a model whereby the Hsp70-Hsp110 chaperone complex antagonizes Cin8 plus-end motility and prevents premature spindle elongation in S phase. ..
  49. Rock J, Amon A. Cdc15 integrates Tem1 GTPase-mediated spatial signals with Polo kinase-mediated temporal cues to activate mitotic exit. Genes Dev. 2011;25:1943-54 pubmed publisher
    ..The MEN GTPase Tem1 has been assumed to be the central switch in MEN regulation...
  50. Park S, Cable A, Blair J, Stockstill K, Shannnon K. Bub2 regulation of cytokinesis and septation in budding yeast. BMC Cell Biol. 2009;10:43 pubmed publisher
    ..Bub2 and its binding partner Bfa1 act as a GTPase activating protein (GAP) to negatively regulate the MEN GTPase Tem1. The Bub2/Bfa1 checkpoint pathway is required to delay the cell cycle in response to mispositioned spindles...