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Gene Review

CDH1  -  Cdh1p

Saccharomyces cerevisiae S288c

Synonyms: APC/C activator protein CDH1, CDC20 homolog 1, HCT1, Homolog of CDC twenty 1, YGL003C
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High impact information on CDH1

  • Viability of hct1 mutants depends on SIC1 [1].
  • Hct1 and the related Cdc20 may function as substrate-specific regulators of proteolysis during mitosis [1].
  • Yeast Hct1 is a regulator of Clb2 cyclin proteolysis [1].
  • Remarkably, elevated levels of Hct1 ectopically activate destruction box- and Cdc23-dependent degradation of Clb2 and cause phenotypic effects characteristic for a depletion of M-phase cyclins [1].
  • Cdc14 activates the degradation of Clb cyclins by dephosphorylating the APC-specificity factor Cdh1 [2].

Biological context of CDH1

  • Overexpression of either CDC20 or CDH1 was sufficient to induce APC-dependent proteolysis of the appropriate target in stages of the cell cycle in which substrates are normally stable [3].
  • Simultaneous deletion of PDS1 and CDH1 caused extensive chromosome missegregation and cell death [4].
  • Exit from mitosis in yeast involves accumulation of the cyclin kinase inhibitor Sic1 as well as cyclin proteolysis mediated by APC/C bound by the activating subunit Cdh1/Hct1 (APC(Cdh1)) [5].
  • Both processes require the Cdc14 phosphatase, whose release from the nucleolus during anaphase causes dephosphorylation and thereby activation of Cdh1 and accumulation of another protein, Sic1 (refs 4-7) [5].
  • Here we show, however, that spindle disassembly and cell division occur without significant APC(Cdc20)-mediated Clb5 degradation, as well as in the absence of both Cdh1 and Sic1 [6].

Anatomical context of CDH1

  • Cdh1 contributes to proper exit from mitosis and maintenance of G(1) phase in eukaryotic cells by activating a large ubiquitin ligase called the anaphase-promoting complex, or cyclosome (APC/C) [7].

Associations of CDH1 with chemical compounds


Physical interactions of CDH1

  • Hsl1p is stabilized by mutations in CDH1 and CDC23, both of which result in compromised APC activity [8].

Enzymatic interactions of CDH1


Regulatory relationships of CDH1

  • Spo12 protein level is regulated by the APC and the protein is degraded in G1 by an Hct1-dependent mechanism [10].

Other interactions of CDH1

  • CDC20 and CDH1: a family of substrate-specific activators of APC-dependent proteolysis [3].
  • Failure to interact with Hct1 resulted in stabilization of Clb2 [11].
  • The model correctly predicted quantitative dependence of cell size on gene dosage of the G1 cyclin CLN3, but it incorrectly predicted strong genetic interactions between G1 cyclins and the anaphase-promoting complex specificity factor Cdh1 [12].
  • We observed that a spo12 mutation is synthetically lethal in vegetative cells with a mutation in HCT1, a gene necessary for cells to exit mitosis, suggesting that Spo12p may have a role in exit from mitosis [13].
  • In G1, Cdc5 itself was degraded by an APC-dependent and Hct1-dependent mechanism [14].


  1. Yeast Hct1 is a regulator of Clb2 cyclin proteolysis. Schwab, M., Lutum, A.S., Seufert, W. Cell (1997) [Pubmed]
  2. Cfi1 prevents premature exit from mitosis by anchoring Cdc14 phosphatase in the nucleolus. Visintin, R., Hwang, E.S., Amon, A. Nature (1999) [Pubmed]
  3. CDC20 and CDH1: a family of substrate-specific activators of APC-dependent proteolysis. Visintin, R., Prinz, S., Amon, A. Science (1997) [Pubmed]
  4. The role of Cdh1p in maintaining genomic stability in budding yeast. Ross, K.E., Cohen-Fix, O. Genetics (2003) [Pubmed]
  5. APC(Cdc20) promotes exit from mitosis by destroying the anaphase inhibitor Pds1 and cyclin Clb5. Shirayama, M., Tóth, A., Gálová, M., Nasmyth, K. Nature (1999) [Pubmed]
  6. APC-dependent proteolysis of the mitotic cyclin Clb2 is essential for mitotic exit. Wäsch, R., Cross, F.R. Nature (2002) [Pubmed]
  7. Multi-kinase phosphorylation of the APC/C activator Cdh1 revealed by mass spectrometry. Hall, M.C., Warren, E.N., Borchers, C.H. Cell Cycle (2004) [Pubmed]
  8. Hsl1p, a Swe1p inhibitor, is degraded via the anaphase-promoting complex. Burton, J.L., Solomon, M.J. Mol. Cell. Biol. (2000) [Pubmed]
  9. Inhibition of APCCdh1 activity by Cdh1/Acm1/Bmh1 ternary complex formation. Dial, J.M., Petrotchenko, E.V., Borchers, C.H. J. Biol. Chem. (2007) [Pubmed]
  10. The Spo12 protein of Saccharomyces cerevisiae: a regulator of mitotic exit whose cell cycle-dependent degradation is mediated by the anaphase-promoting complex. Shah, R., Jensen, S., Frenz, L.M., Johnson, A.L., Johnston, L.H. Genetics (2001) [Pubmed]
  11. Yeast Hct1 recognizes the mitotic cyclin Clb2 and other substrates of the ubiquitin ligase APC. Schwab, M., Neutzner, M., Möcker, D., Seufert, W. EMBO J. (2001) [Pubmed]
  12. Testing a mathematical model of the yeast cell cycle. Cross, F.R., Archambault, V., Miller, M., Klovstad, M. Mol. Biol. Cell (2002) [Pubmed]
  13. Genetic and biochemical characterization of the yeast spo12 protein. Grether, M.E., Herskowitz, I. Mol. Biol. Cell (1999) [Pubmed]
  14. The Polo-related kinase Cdc5 activates and is destroyed by the mitotic cyclin destruction machinery in S. cerevisiae. Charles, J.F., Jaspersen, S.L., Tinker-Kulberg, R.L., Hwang, L., Szidon, A., Morgan, D.O. Curr. Biol. (1998) [Pubmed]
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