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Gene Review

CLN3  -  Cln3p

Saccharomyces cerevisiae S288c

Synonyms: DAF1, FUN10, G1/S-specific cyclin CLN3, WHI1, YAL040C
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Disease relevance of CLN3


High impact information on CLN3


Biological context of CLN3


Anatomical context of CLN3


Associations of CLN3 with chemical compounds

  • Transcription of the CLN3 G(1) cyclin in Saccharomyces cerevisiae is positively regulated by glucose in a process that involves a set of DNA elements with the sequence AAGAAAAA (A(2)GA(5)) [15].
  • The growth rate dependency of trehalose accumulation was supported by studies in cells overexpressing the G(1)-cyclin CLN3 [16].
  • Replacing Ser72 with Asp, to mimic phosphorylation at an optimal Cdk-consensus site located in the first SH3 domain of Bem1p, suppressed vacuolar fragmentation in cells lacking Cln3p [17].
  • Cln3 Delta, far1 Delta, and strains overexpressing Far1 do not delay budding during an ethanol glucose shift-up as wild type does [18].
  • The strain containing Cln3-1 was found to be resistant to cell cycle arrest induced by exogenous phytosphingosine, indicating that Cln3 acts downstream of the sphingoid bases in this response [19].

Physical interactions of CLN3

  • We conclude that AZF1 is a glucose-dependent transcription factor that interacts with the CLN3 A(2)GA(5) repeats to play a positive role in the regulation of CLN3 mRNA expression by glucose [15].
  • Whi3 binds the mRNA of the G1 cyclin CLN3 to modulate cell fate in budding yeast [20].

Enzymatic interactions of CLN3

  • Cln3 associates with Cdc28 to form an active kinase complex that phosphorylates Cln3 itself and a co-precipitated substrate of 45 kDa [21].

Regulatory relationships of CLN3

  • First, we show that CLN3 alone is sufficient to maximally activate CLN2 transcription [22].
  • Using in vivo and in vitro assays, we found that Cln3p was unable to promote vacuole fusion in the absence of Bem1p or in the presence of a nonphosphorylatable Bem1p-Ser72Ala mutant [17].
  • Furthermore, activation of Cdc42p also suppressed vacuolar fragmentation in the absence of Cln3p [17].
  • The G(1) cyclin Cln3 promotes cell cycle entry via the transcription factor Swi6 [23].
  • Azf1 activates CLN3 transcription in Saccharomyces cerevisiae cells growing in glucose [24].

Other interactions of CLN3

  • The activated mutation, CLN3-2, partially suppresses the growth defect of sgv1, suggesting that the SGV1 and CLN3 proteins may act in the same growth control pathway [5].
  • Here we report our finding that the G(1) cyclin Cln3 and the S cyclin Clb5 are the key factors required for recovery from heat shock-induced G(1) arrest [25].
  • Furthermore, elevated MBP1, a transcriptional regulator of cyclins, altered the transcriptional start site in CLN3 mRNA, shifting it 45 nucleotides upstream of the normal [26].
  • Activation of SBF and MBF depends on the G(1) cyclin Cln3 and a largely uncharacterized protein called Bck2 [27].
  • Several of these mutants identified previously known genes, including CLN3, FUS3, and FAR1 [28].
  • Ydj1 is limiting for release of Cln3 and timely entry into the cell cycle [29].

Analytical, diagnostic and therapeutic context of CLN3

  • As shown by indirect immunofluorescence and biochemical fractionation, Cln3p localization appears to be primarily nuclear, with the most obvious accumulation of Cln3p to the nuclei of large budded cells [30].



  1. Human D-type cyclin. Xiong, Y., Connolly, T., Futcher, B., Beach, D. Cell (1991) [Pubmed]
  2. Cln3 activates G1-specific transcription via phosphorylation of the SBF bound repressor Whi5. de Bruin, R.A., McDonald, W.H., Kalashnikova, T.I., Yates, J., Wittenberg, C. Cell (2004) [Pubmed]
  3. CLN3 functions in both daughter and mother cells of S. cerevisiae. Linskens, M., Tyers, M., Futcher, B. Cell (1993) [Pubmed]
  4. 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]
  5. SGV1 encodes a CDC28/cdc2-related kinase required for a G alpha subunit-mediated adaptive response to pheromone in S. cerevisiae. Irie, K., Nomoto, S., Miyajima, I., Matsumoto, K. Cell (1991) [Pubmed]
  6. A novel Mcm1-dependent element in the SWI4, CLN3, CDC6, and CDC47 promoters activates M/G1-specific transcription. McInerny, C.J., Partridge, J.F., Mikesell, G.E., Creemer, D.P., Breeden, L.L. Genes Dev. (1997) [Pubmed]
  7. Early cell cycle box-mediated transcription of CLN3 and SWI4 contributes to the proper timing of the G(1)-to-S transition in budding yeast. MacKay, V.L., Mai, B., Waters, L., Breeden, L.L. Mol. Cell. Biol. (2001) [Pubmed]
  8. Saccharomyces cerevisiae G1 cyclins differ in their intrinsic functional specificities. Levine, K., Huang, K., Cross, F.R. Mol. Cell. Biol. (1996) [Pubmed]
  9. Osmotic stress causes a G1 cell cycle delay and downregulation of Cln3/Cdc28 activity in Saccharomyces cerevisiae. Bellí, G., Garí, E., Aldea, M., Herrero, E. Mol. Microbiol. (2001) [Pubmed]
  10. Multiple pathways for suppression of mutants affecting G1-specific transcription in Saccharomyces cerevisiae. Flick, K., Wittenberg, C. Genetics (2005) [Pubmed]
  11. Saccharomyces cerevisiae lacking Btn1p modulate vacuolar ATPase activity to regulate pH imbalance in the vacuole. Padilla-López, S., Pearce, D.A. J. Biol. Chem. (2006) [Pubmed]
  12. Coupling of cell division to cell growth by translational control of the G1 cyclin CLN3 in yeast. Polymenis, M., Schmidt, E.V. Genes Dev. (1997) [Pubmed]
  13. The molecular chaperone Ydj1 is required for the p34CDC28-dependent phosphorylation of the cyclin Cln3 that signals its degradation. Yaglom, J.A., Goldberg, A.L., Finley, D., Sherman, M.Y. Mol. Cell. Biol. (1996) [Pubmed]
  14. The G1 cyclin Cln3p controls vacuolar biogenesis in Saccharomyces cerevisiae. Han, B.K., Aramayo, R., Polymenis, M. Genetics (2003) [Pubmed]
  15. AZF1 is a glucose-dependent positive regulator of CLN3 transcription in Saccharomyces cerevisiae. Newcomb, L.L., Hall, D.D., Heideman, W. Mol. Cell. Biol. (2002) [Pubmed]
  16. Trehalose and glycogen accumulation is related to the duration of the G1 phase of Saccharomyces cerevisiae. Paalman, J.W., Verwaal, R., Slofstra, S.H., Verkleij, A.J., Boonstra, J., Verrips, C.T. FEMS Yeast Res. (2003) [Pubmed]
  17. Bem1p, a scaffold signaling protein, mediates cyclin-dependent control of vacuolar homeostasis in Saccharomyces cerevisiae. Han, B.K., Bogomolnaya, L.M., Totten, J.M., Blank, H.M., Dangott, L.J., Polymenis, M. Genes Dev. (2005) [Pubmed]
  18. A cell sizer network involving Cln3 and Far1 controls entrance into S phase in the mitotic cycle of budding yeast. Alberghina, L., Rossi, R.L., Querin, L., Wanke, V., Vanoni, M. J. Cell Biol. (2004) [Pubmed]
  19. Role for de novo sphingoid base biosynthesis in the heat-induced transient cell cycle arrest of Saccharomyces cerevisiae. Jenkins, G.M., Hannun, Y.A. J. Biol. Chem. (2001) [Pubmed]
  20. Whi3 binds the mRNA of the G1 cyclin CLN3 to modulate cell fate in budding yeast. Garí, E., Volpe, T., Wang, H., Gallego, C., Futcher, B., Aldea, M. Genes Dev. (2001) [Pubmed]
  21. The Cln3-Cdc28 kinase complex of S. cerevisiae is regulated by proteolysis and phosphorylation. Tyers, M., Tokiwa, G., Nash, R., Futcher, B. EMBO J. (1992) [Pubmed]
  22. CLN3, not positive feedback, determines the timing of CLN2 transcription in cycling cells. Stuart, D., Wittenberg, C. Genes Dev. (1995) [Pubmed]
  23. The G(1) cyclin Cln3 promotes cell cycle entry via the transcription factor Swi6. Wijnen, H., Landman, A., Futcher, B. Mol. Cell. Biol. (2002) [Pubmed]
  24. The function and properties of the Azf1 transcriptional regulator change with growth conditions in Saccharomyces cerevisiae. Slattery, M.G., Liko, D., Heideman, W. Eukaryotic Cell (2006) [Pubmed]
  25. Recovery of the yeast cell cycle from heat shock-induced G(1) arrest involves a positive regulation of G(1) cyclin expression by the S phase cyclin Clb5. Li, X., Cai, M. J. Biol. Chem. (1999) [Pubmed]
  26. Overexpression of eIF4E in Saccharomyces cerevisiae causes slow growth and decreased alpha-factor response through alterations in CLN3 expression. Anthony, C., Zong, Q., De Benedetti, A. J. Biol. Chem. (2001) [Pubmed]
  27. 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]
  28. Identification and characterization of FAR3, a gene required for pheromone-mediated G1 arrest in Saccharomyces cerevisiae. Horecka, J., Sprague, G.F. Genetics (1996) [Pubmed]
  29. Cyclin Cln3 is retained at the ER and released by the J chaperone Ydj1 in late G1 to trigger cell cycle entry. Vergés, E., Colomina, N., Garí, E., Gallego, C., Aldea, M. Mol. Cell (2007) [Pubmed]
  30. Distinct subcellular localization patterns contribute to functional specificity of the Cln2 and Cln3 cyclins of Saccharomyces cerevisiae. Miller, M.E., Cross, F.R. Mol. Cell. Biol. (2000) [Pubmed]
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