... is a common feature of cancer cells, and thus a potentially important therapeutic target. Here, we show that cyclin-dependent kinase (CDK)-induced replication stress, resulting from Wee1 inactivation, is synthetic lethal with mutations disrupting dNTP homeostasis in fission yeast. Wee1 inactivation leads...

...Cui Qiu; Yuan-yuan Yi; Rafael Lucena; Meng-juan Wu; Jia-hao Sun; Xi Wang; Quan-wen Jin; Yamei Wang ABSTRACT The key cyclin-dependent kinase Cdk1 (Cdc2) promotes irreversible mitotic entry, mainly by activating the phosphatase Cdc25 while suppressing the tyrosine kinase Wee1. Wee1 needs...

... and the positioning of the division plane. Cdr2 forms nodes on the medial cortex containing factors that constitute an inhibitory pathway for Wee1. This pathway is regulated by polar gradients of the DYRK kinase Pom1, and involves a direct inhibitor of Wee1, the SAD kinase Cdr1. Cdr2 also interacts with the anillin...

...-interacting tryptophan provides Torin1 resistance, confirming the specificity of Torin1 for TOR. Using this mutation, we show that Torin1 advanced mitotic onset before inducing growth arrest. In contrast to TOR inhibition with rapamycin, regulation by either Wee1 or Cdc25 was sufficient for this Torin1...

... a link between dnt1 + and wee1 + . Furthermore, we showed that elevated protein levels of the mitotic inhibitor Wee1 kinase and the corresponding attenuation in Cdk1 activity is responsible for the rescuing effect of dnt1Δ on SIN mutants. Finally, our data also suggest that Dnt1 modulates Wee1 activity...

... the kinase domain markedly increased the sensitivities of the analogue-sensitive kinases to ATP analogues in three out of five S. pombe kinases (i.e. Plo1, Orb5 and Wee1) that harbor this conserved methionine residue. Kinome alignment established that a methionine residue is found at this site in 5–9...

... correct mitotic entry and exit. In this work, we studied the regulatory mechanisms controlling the cyclin-B–Cdc2 and PP2A balance by analysing the activity of the Greatwall kinase and PP2A, and the different components of the MPF amplification loop (Myt1, Wee1, Cdc25) during the first embryonic cell cycle...

... gene to estrogen. S. pombe cells deleted for ini1 + fail to form colonies and arrest with an elongated cell phenotype, indicating a cell cycle block. Cell cycle arrest is dependent on expression of Wee1, but not Rad3, suggesting that it occurs independently of the DNA damage checkpoint control...

...Douglas R. Kellogg Wee1-related kinases function in a highly conserved mechanism that controls the timing of entry into mitosis. Loss of Wee1 function causes fission yeast and budding yeast cells to enter mitosis before sufficient growth has occurred, leading to formation of daughter cells...

... reported that overexpression of Chk1p causes a wee1 + -dependent G 2 arrest, and this or irradiation leads to hyperphosphorylation of Wee1p. Moreover, Chk1p directly phosphorylates Wee1p in vitro. These data suggested that Wee1p is a key target of Chk1p action in checkpoint control. However, cells lacking...

...Véronique Baldin; Bernard Ducommun ABSTRACT Wee1 kinase-dependent phosphorylation of cdc2 maintains the cdc2/cyclin B complex in an inert form until it is activated by the cdc25 tyrosine phosphatase at the end of G 2 . As described for cdc25, cell cycle-linked changes in the intracellular...

... stimulates its own production by activating Cdc25 and inhibiting Wee1) and a negative feedback loop (MPF stimulates its own destruction by indirectly activating the ubiquitin pathway that degrades its cyclin subunit). To uncover the full dynamical possibilities of the control system, we translate...