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Gene Review

CLN2  -  Cln2p

Saccharomyces cerevisiae S288c

Synonyms: G1/S-specific cyclin CLN2, YPL256C
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Disease relevance of CLN2


High impact information on CLN2

  • Mutational analysis of FAR1 reveals a correlation between its ability to associate with CDC28-CLN2 and to arrest the cell cycle [2].
  • In daughter cells, transcription of CLN1 and CLN2 is induced in a size-dependent manner, and these cyclins are necessary for the normal timing of cell cycle initiation [3].
  • Thus, CLN function and CDC28 activity jointly stimulate CLN1 and CLN2 mRNA levels, potentially forming a positive feedback loop for CLN1 and CLN2 expression [4].
  • A potential positive feedback loop controlling CLN1 and CLN2 gene expression at the start of the yeast cell cycle [4].
  • An internally deleted nonfunctional cln2 gene was used as a reporter gene to demonstrate that in the absence of mating pheromone, efficient expression of cln2 mRNA requires both an active CDC28 gene and at least one functional CLN gene. mRNA from a nonfunctional cln1 gene was regulated similarly [4].

Biological context of CLN2

  • We thus propose that FAR1 contributes to cell cycle arrest by inhibiting CLN2 [5].
  • CLN2 overexpression suppressed the constitutive signaling and division-arrest phenotypes of cells with a disrupted gpa1 gene, indicating that the site of action for repression is downstream of the alpha-subunit (Gpa1p) of the heterotrimeric G protein [6].
  • FAR1 is required for posttranscriptional regulation of CLN2 gene expression in response to mating pheromone [7].
  • These results imply that CLN1 and CLN2 have a role in the regulation of DNA replication [8].
  • Rme1 induces CLN2, and we show that it has a haploid-specific role in regulating cell size and pheromone sensitivity [9].

Anatomical context of CLN2


Associations of CLN2 with chemical compounds

  • The cells treated with exogenous AdoMet and AdoHcy had markedly decreased levels of SWE1 and CLN2 mRNA, providing the basis for the suppression of the Ca(2+) sensitivity by the sah1-1 mutation [12].
  • Consistent with this, release from pheromone arrest (where CLN1 and CLN2 are not expressed) in cycloheximide shows no induction at all [13].
  • Cell cycle-regulated transcriptional activation/inactivation of the CLN2 promoter was also discernible with yEGFP3- Cln2(PEST), using cultures that were previously synchronized with nocodazole [14].
  • We suggest that differential regulation of CLN1 and CLN2 by glucose results from differences in the capacity of SBF to activate transcription driven by SCB and MCB core elements [15].
  • The DEM-induced G1 arrest requires a properly regulated RAS pathway and can be bypassed by overexpressing the G1-specific cyclin CLN2 [16].

Physical interactions of CLN2

  • Swi4 may bind to nonconsensus sequences in the CLN2 promoter (possibly in addition to consensus sites), or it may act indirectly to regulate CLN2 expression [17].
  • This assay may be useful for distinguishing genes that promote directly the posttranslational assembly of active Cln2p/Cdc28p kinase complexes from those that stimulate the accumulation of active complexes via a positive-feedback loop that governs synthesis of G1 cyclins [10].
  • We show that fusion of the Cln2 domain to a stabilized form of the cyclin-dependent kinase inhibitor Sic1 (Delta N-Sic1), a substrate of SCF(Cdc4), results in degradation in a phosphorylation-dependent manner [18].
  • Cks1 can both stabilize Cln2-Cdc28 complexes and activate intact complexes in vitro, suggesting that it plays multiple roles in the biogenesis of active G(1) cyclin-CDK complexes [19].
  • An essential function of Grr1 for the degradation of Cln2 is to act as a binding core that links Cln2 to Skp1 [20].

Enzymatic interactions of CLN2

  • These data suggest that Grr1 is required for degradation of Cln2 through linking phosphorylated Cln2 to Skp1 in a SCFGrr1 complex [20].

Regulatory relationships of CLN2

  • Overexpression of the G1-cyclin gene CLN2 represses the mating pathway in Saccharomyces cerevisiae at the level of the MEKK Ste11 [21].
  • Here we show that deletion of the Saccharomyces cerevisiae G1 cyclins CLN1 and CLN2 suppressed the essential requirement for MEC1 function [22].
  • PSA1 is an essential gene, and PSA1 transcription is nearly co-ordinately regulated with CLN2 transcription, peaking near START [23].
  • First, we show that CLN3 alone is sufficient to maximally activate CLN2 transcription [24].
  • A yeast strain with a defective mitosis regulating BUB3 gene showed increased ART sensitivity and another strain with a defective proliferation-regulating CLN2 gene showed increased ART resistance over the wild-type strain, wt644 [25].

Other interactions of CLN2

  • Identification of a gene necessary for cell cycle arrest by a negative growth factor of yeast: FAR1 is an inhibitor of a G1 cyclin, CLN2 [5].
  • We find that stimulation of the Ras/cAMP pathway represses expression of CLN1, CLN2 and co-regulated genes, inhibiting Start [26].
  • OSS1 is important for the transcriptional repression of SWE1 and CLN2 in G2 [27].
  • Swi4 activates transcription of many genes at the G1-S transition, including CLN1 and CLN2 [28].
  • Cln3-associated kinase is therefore likely to have an intrinsic in vivo substrate specificity distinct from that of Cln2-associated kinase, despite their functional redundancy [29].

Analytical, diagnostic and therapeutic context of CLN2


  1. Human D-type cyclin. Xiong, Y., Connolly, T., Futcher, B., Beach, D. Cell (1991) [Pubmed]
  2. FAR1 links the signal transduction pathway to the cell cycle machinery in yeast. Peter, M., Gartner, A., Horecka, J., Ammerer, G., Herskowitz, I. Cell (1993) [Pubmed]
  3. Different G1 cyclins control the timing of cell cycle commitment in mother and daughter cells of the budding yeast S. cerevisiae. Lew, D.J., Marini, N.J., Reed, S.I. Cell (1992) [Pubmed]
  4. A potential positive feedback loop controlling CLN1 and CLN2 gene expression at the start of the yeast cell cycle. Cross, F.R., Tinkelenberg, A.H. Cell (1991) [Pubmed]
  5. Identification of a gene necessary for cell cycle arrest by a negative growth factor of yeast: FAR1 is an inhibitor of a G1 cyclin, CLN2. Chang, F., Herskowitz, I. Cell (1990) [Pubmed]
  6. G1 cyclins CLN1 and CLN2 repress the mating factor response pathway at Start in the yeast cell cycle. Oehlen, L.J., Cross, F.R. Genes Dev. (1994) [Pubmed]
  7. FAR1 is required for posttranscriptional regulation of CLN2 gene expression in response to mating pheromone. Valdivieso, M.H., Sugimoto, K., Jahng, K.Y., Fernandes, P.M., Wittenberg, C. Mol. Cell. Biol. (1993) [Pubmed]
  8. Mutations in RAD27 define a potential link between G1 cyclins and DNA replication. Vallen, E.A., Cross, F.R. Mol. Cell. Biol. (1995) [Pubmed]
  9. Genetic analysis of the shared role of CLN3 and BCK2 at the G(1)-S transition in Saccharomyces cerevisiae. Wijnen, H., Futcher, B. Genetics (1999) [Pubmed]
  10. G1 cyclin-dependent activation of p34CDC28 (Cdc28p) in vitro. Deshaies, R.J., Kirschner, M. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  11. Efficient selection of hybrids by protoplast fusion using drug resistance markers and reporter genes in Saccharomyces cerevisiae. Nakazawa, N., Iwano, K. J. Biosci. Bioeng. (2004) [Pubmed]
  12. Involvement of S-adenosylmethionine in G1 cell-cycle regulation in Saccharomyces cerevisiae. Mizunuma, M., Miyamura, K., Hirata, D., Yokoyama, H., Miyakawa, T. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  13. Direct induction of G1-specific transcripts following reactivation of the Cdc28 kinase in the absence of de novo protein synthesis. Marini, N.J., Reed, S.I. Genes Dev. (1992) [Pubmed]
  14. Destabilized green fluorescent protein for monitoring dynamic changes in yeast gene expression with flow cytometry. Mateus, C., Avery, S.V. Yeast (2000) [Pubmed]
  15. Regulation of cell size by glucose is exerted via repression of the CLN1 promoter. Flick, K., Chapman-Shimshoni, D., Stuart, D., Guaderrama, M., Wittenberg, C. Mol. Cell. Biol. (1998) [Pubmed]
  16. In budding yeast, reactive oxygen species induce both RAS-dependent and RAS-independent cell cycle-specific arrest. Wanke, V., Accorsi, K., Porro, D., Esposito, F., Russo, T., Vanoni, M. Mol. Microbiol. (1999) [Pubmed]
  17. Role of Swi4 in cell cycle regulation of CLN2 expression. Cross, F.R., Hoek, M., McKinney, J.D., Tinkelenberg, A.H. Mol. Cell. Biol. (1994) [Pubmed]
  18. Transferable domain in the G(1) cyclin Cln2 sufficient to switch degradation of Sic1 from the E3 ubiquitin ligase SCF(Cdc4) to SCF(Grr1). Berset, C., Griac, P., Tempel, R., La Rue, J., Wittenberg, C., Lanker, S. Mol. Cell. Biol. (2002) [Pubmed]
  19. Cks1 is required for G(1) cyclin-cyclin-dependent kinase activity in budding yeast. Reynard, G.J., Reynolds, W., Verma, R., Deshaies, R.J. Mol. Cell. Biol. (2000) [Pubmed]
  20. An essential function of Grr1 for the degradation of Cln2 is to act as a binding core that links Cln2 to Skp1. Kishi, T., Yamao, F. J. Cell. Sci. (1998) [Pubmed]
  21. Overexpression of the G1-cyclin gene CLN2 represses the mating pathway in Saccharomyces cerevisiae at the level of the MEKK Ste11. Wassmann, K., Ammerer, G. J. Biol. Chem. (1997) [Pubmed]
  22. Interaction between the MEC1-dependent DNA synthesis checkpoint and G1 cyclin function in Saccharomyces cerevisiae. Vallen, E.A., Cross, F.R. Genetics (1999) [Pubmed]
  23. Over-expression of S. cerevisiae G1 cyclins restores the viability of alg1 N-glycosylation mutants. Benton, B.K., Plump, S.D., Roos, J., Lennarz, W.J., Cross, F.R. Curr. Genet. (1996) [Pubmed]
  24. CLN3, not positive feedback, determines the timing of CLN2 transcription in cycling cells. Stuart, D., Wittenberg, C. Genes Dev. (1995) [Pubmed]
  25. The anti-malarial artesunate is also active against cancer. Efferth, T., Dunstan, H., Sauerbrey, A., Miyachi, H., Chitambar, C.R. Int. J. Oncol. (2001) [Pubmed]
  26. Inhibition of G1 cyclin activity by the Ras/cAMP pathway in yeast. Tokiwa, G., Tyers, M., Volpe, T., Futcher, B. Nature (1994) [Pubmed]
  27. A search for proteins that interact genetically with histone H3 and H4 amino termini uncovers novel regulators of the Swe1 kinase in Saccharomyces cerevisiae. Ma, X.J., Lu, Q., Grunstein, M. Genes Dev. (1996) [Pubmed]
  28. A role for the Pkc1 MAP kinase pathway of Saccharomyces cerevisiae in bud emergence and identification of a putative upstream regulator. Gray, J.V., Ogas, J.P., Kamada, Y., Stone, M., Levin, D.E., Herskowitz, I. EMBO J. (1997) [Pubmed]
  29. Saccharomyces cerevisiae G1 cyclins differ in their intrinsic functional specificities. Levine, K., Huang, K., Cross, F.R. Mol. Cell. Biol. (1996) [Pubmed]
  30. Rapid degradation of the G1 cyclin Cln2 induced by CDK-dependent phosphorylation. Lanker, S., Valdivieso, M.H., Wittenberg, C. Science (1996) [Pubmed]
  31. Identification of novel and conserved functional and structural elements of the G1 cyclin Cln3 important for interactions with the CDK Cdc28 in Saccharomyces cerevisiae. Miller, M.E., Cross, F.R., Groeger, A.L., Jameson, K.L. Yeast (2005) [Pubmed]
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