Disease relevance of cut4

• Mutations in cut4 result in hypersensitivity to cyclic AMP and to stress-inducing heavy metals, inhibition of the onset of anaphase, disruption of the 20S complex, and inhibition of mitotic cyclin ubiquitination [1].

High impact information on cut4

• The rapid degradation of Cut2 at anaphase requires its amino-terminal region and the activity of Cut9 (ref. 14), a component of the 20S cyclosome/anaphase-promoting complex (APC), which is necessary for cyclin destruction [2].
• Loss of the anaphase-promoting complex in quiescent cells causes unscheduled hepatocyte proliferation [3].
• The anaphase-promoting complex: it's not just for mitosis any more [4].
• However, an abnormal spindle and/or unattached kinetochores activates a conserved spindle checkpoint that blocks APC function [5].
• The results suggest that dual downregulation of CDK, one via the APC and the other via the CDK inhibitor, is a universal mechanism that is used to arrest cell cycle progression at G1 [6].

Biological context of cut4

• At the restrictive temperature of 36 degrees C, lid1-6 mutant cells arrest with a "cut" phenotype similar to that of cut4 and cut9 mutants [7].
• The 20S cyclosome complex (also known as the anaphase-promoting complex) has ubiquitin ligase activity and is required for mitotic cyclin destruction and sister chromatid separation [1].
• Moreover, we demonstrate that cyclin-dependent kinase phosphorylation sites adjacent to the C-box may regulate the interaction with the APC [8].
• The binding site for Pus1 was mapped to a cluster of repetitive sequences also found in the proteasome subunit SpRpn2 and the anaphase-promoting complex/cyclosome (APC/C) subunit Cut4 [9].
• The spindle checkpoint coordinates cell cycle progression and chromosome segregation by inhibiting anaphase promoting complex/cyclosome until all kinetochores interact with the spindle properly [10].

Anatomical context of cut4

• Genetic and biochemical experiments with several different organisms have documented that polo-like kinases are involved in many aspects of the cell cycle, such as activation of Cdc2, centrosome assembly and maturation, activation of the anaphase-promoting complex (APC) during the metaphase-anaphase transition, and cytokinesis [11].

Associations of cut4 with chemical compounds

• DNA rereplication can also be induced in cells that enter mitosis prematurely because of lack of tyrosine phosphorylation of NIMX(cdc2) and impaired anaphase-promoting complex function [12].
• Overexpression of Mad2p or inactivation of Slp1p, a regulator of the anaphase-promoting complex, also rescued the checkpoint defect of HU-treated rad3 cells [13].

Analytical, diagnostic and therapeutic context of cut4

• In synchronized Arabidopsis cell cultures the cdc20 transcripts were present from early G2 until the M-phase exit, ccs52B from G2/M to M while ccs52A1 and ccs52A2 were from late M until early G2, suggesting consecutive action of these APC activators in the plant cell cycle [14].

References