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

• In total, at least 19 serine and threonine residues on Cdh1 are phosphorylated in vivo [7].

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

• The addition of Acm1 decreases Clb2 ubiquitination when using either phosphorylated or nonphosphorylated Cdh1 [9].

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].

References