Disease relevance of cdc2

• Inhibition of small G proteins by clostridium sordellii lethal toxin activates cdc2 and MAP kinase in Xenopus oocytes [1].

High impact information on cdc2

• However, p72 directly associates with cdc2-cyclin B in a cell cycle-dependent manner, reaching a peak at M phase [2].
• Oscillation of MPF is accompanied by periodic association between cdc25 and cdc2-cyclin B [2].
• The cdc25 protein is a highly specific tyrosine phosphatase that triggers mitosis by dephosphorylating the cdc2 protein kinase [3].
• Our results indicate that in higher eukaryotes, DNA replication (G1-S) and mitosis (G2-M) may be controlled by distinctly different cdc2 proteins [4].
• In some organisms the activation of the kinase at the G2/M boundary is due to dephosphorylation of a highly conserved tyrosine residue at position 15 (Y15) of the cdc2 protein [5].

Biological context of cdc2

• Ablation of cyclin A messenger RNA in cytostatic factor/metaphase-arrested extracts of Xenopus eggs, followed by in vitro progression into interphase, resulted in the premature appearance of cyclin B-cdc2-associated H1 kinase activity and premature entry into mitosis [6].
• Kinetic studies demonstrate the concentration of cyclin A added does not affect the 10 min lag period required for kinase activation or the timing of maximal activity, but does control the rate of deactivation of cdc2 kinase during exit from mitosis [7].
• The 42-kD cyclin was also produced by the digestion of native cyclin B forming a complex with cdc2, a catalytic subunit of MPF, and a fragment transiently appeared during cyclin degradation when eggs were released from metaphase II arrest by egg activation [8].
• Suppressing down-regulation of MAPK at fertilization, for example by constitutively activating the upstream MAPK cascade, specifically suppresses cyclin B-cdc2 kinase activation and its consequence, entry into first mitosis [9].
• Phosphorylation of cyclin B1 is not required for cdc2 binding or cdc2 kinase activity [10].

Anatomical context of cdc2

• These two events do not depend upon formation of a new complex between cyclin and cdc2 protein kinase, since these two proteins are already found associated in resting oocytes, prior to activation of the kinase [11].
• The cortical localization of cdc2 is dependent upon both microtubules and microfilaments [12].
• The cytoskeleton-dependent localization of cdc2/cyclin B in blastomere cortex during Xenopus embryonic cell cycle [12].
• At the 8th cell cycle, most of the cdc2/cyclin B was localized in the cortical cytoplasm throughout the cell cycle, in the centrosomes and the nucleus at interphase and prometaphase, and in the spindles at metaphase and anaphase [12].
• These data suggest that phosphorylation of DLIC by cdc2 kinase leads directly to the loss of membrane-associated CD and an inhibition of organelle movement [13].

Associations of cdc2 with chemical compounds

• Using extracts prepared from cycloheximide-arrested interphase cells, we show that although p42MAPK activation can occur in response to cyclin-activated cdc2, the Ras-induced activation of p42MAPK occurs without intervening cdc2 activation [14].
• Several of the cdc2 mutants were found to affect the kinetics of cyclin B1 and/or mos-induced GVBD upon coinjection, although none affected the rate of progesterone-induced maturation [15].
• Brefeldin A activation of cdc2 protein kinase occurs with a long time course [16].
• When the blastomeres were treated with nocodazole or latrunculin A at the 8th cell cycle, the amount of cortical cdc2 decreased, but that of cyclin B did not change [12].
• MBP-Mos did not delay DNA replication or the translation of cyclins A or B; it did, however, result in the marked accumulation of tyrosine phosphorylated cdc2 [17].

Physical interactions of cdc2

• Porcine brain neurofilament-H tail domain kinase: its identification as cdk5/p26 complex and comparison with cdc2/cyclin B kinase [18].

Enzymatic interactions of cdc2

• (ii) Endogenous cdc25 is phosphorylated on Ser-287 in oocytes and dephosphorylated in response to progesterone just before cdc2 dephosphorylation and M-phase entry [19].

Regulatory relationships of cdc2

• These results indicate that Eg1 is regulated by a cell cycle clock independently of cyclin and cdc2 kinase [20].
• Phosphorylation at Tyr 15 and Thr 14 are believed to inhibit the kinase activity of cdc2 [21].

Other interactions of cdc2

• Progesterone-treated G2/prophase oocytes injected with anti-Emi1 antibody fail to activate Maturation Promoting Factor (MPF), a complex of cdc2/cyclin B, and the MAPK pathway, and do not undergo germinal vesicle breakdown (GVBD) [22].
• We show that maturation-promoting factor (Cyclin B/cdc2) cannot itself be responsible for the phosphorylation and activation of PARP in maturing X. laevis eggs [23].
• Inhibition of cdc2 activation by INH/PP2A [24].
• c-mos and cdc2 cooperate in the translational activation of fibroblast growth factor receptor-1 during Xenopus oocyte maturation [25].
• Specifically, we have shown that a purified membrane fraction, in the absence of cytoplasm, can promote phosphorylation of cdc2 on both Thr 14 and Tyr 15 [21].

Analytical, diagnostic and therapeutic context of cdc2

• Microinjection of antisense oligonucleotides to c-mosXe was used to demonstrate the role of mos protein synthesis in the induction of GVBD by the Ala-14/Phe-15 cdc2 mutant [15].
• To investigate the role of cyclin B phosphorylation, we replaced putative cdc2 kinase phosphorylation sites in Xenopus cyclins B1 and B2 by using oligonucleotide site-directed mutagenesis [26].

References