ArticleThe EMBO journal1993
Human Wee1 kinase inhibits cell division by phosphorylating p34cdc2 exclusively on Tyr15.
Article in The EMBO journal, 1993. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 199 papers.
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Who cites it
199 citing papers in PubMed, 485 citations in OpenAlex.
- WEE1 opposes APC/CNature · 2026Article
- Chromosome condensation mechanically primes the nucleus for mitosis.The EMBO journal · 2026Article
- WEE1 stabilizes MYC to promote therapeutic resistance in esophageal adenocarcinoma.Cancer letters · 2026Article
- Proteomics analysis reveals progesterone receptor induced mitochondria-mediated apoptosis in breast cancer cells.Scientific reports · 2025Article
- Mechanism of RPA phosphocode priming and tuning by CDK1/WEE1 signaling circuit.Nature communications · 2025Article
- Article
- Campylobacter jejuni regulates cell cycle progression to potentiate host cell invasion.Cell communication and signaling : CCS · 2025Article
- Regulation of cell cycle in plant gametes: when is the right time to divide?Development (Cambridge, England) · 2025Review
- AZD1775 synergizes with SLC7A11 inhibition to promote ferroptosis.Science China. Life sciences · 2025Article
- Transcriptomic analysis reveals the inhibitory effect of beta-sitosterol on proliferation of bovine preadipocytes.Animal biotechnology · 2024Article
- The Potential for Targeting GCancers · 2024Review
- HPLC, NMR Based Characterization, Antioxidant and Anticancer Activities of Chemical Constituents from Therapeutically Active Fungal Endophytes.Journal of microbiology and biotechnology · 2024Article
- The dynamic role of nucleoprotein SHCBP1 in the cancer cell cycle and its potential as a synergistic target for DNA-damaging agents in cancer therapy.Cell communication and signaling : CCS · 2024Article
- FBH1 deficiency sensitizes cells to WEE1 inhibition by promoting mitotic catastrophe.DNA repair · 2024Article
- Ribonucleotide reductase M2 (RRM2): Regulation, function and targeting strategy in human cancer.Genes & diseases · 2024Review
- Phosphorylation of Bub1 by Mph1 promotes Bub1 signaling at the kinetochore to ensure accurate chromosome segregation.The Journal of biological chemistry · 2024Article
- Ginger Root Bioactive Compounds Specifically Inhibits Growth of Colon Cancer Cells in Culture.Nutrition and metabolic insights · 2024Article
- Combination therapy with WEE1 inhibition and trifluridine/tipiracil against esophageal squamous cell carcinoma.Cancer science · 2023Article
- Synthetic lethal interaction between WEE1 and PKMYT1 is a target for multiple low-dose treatment of high-grade serous ovarian carcinoma.NAR cancer · 2023Article
- Synthetic and Medicinal Chemistry Approaches Toward WEE1 Kinase Inhibitors and Its Degraders.ACS omega · 2023Review
139 more citing papers are in PubMed but not listed here.
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
In fission yeast, the M-phase inducing kinase, a complex of p34cdc2 and cyclin B, is maintained in an inhibited state during interphase due to the phosphorylation of Cdc2 at Tyr15. This phosphorylation is believed to be carried out primarily by the Wee1 kinase. In human cells the negative regulation of p34cdc2/cyclin B is more complex, in that Cdc2 is phosphorylated at two inhibitory sites, Thr14 and Tyr15. The identities of the kinases that phosphorylate these sites are unknown. Since fission yeast Wee1 kinase behaves as a dual-specificity kinase in vitro, a popular hypothesis is that a human Wee1 homolog might phosphorylate p34cdc2 at both sites. We report here that a human gene, identified as a possible Wee1 homologue, blocks cell division when overexpressed in HeLa cells. This demonstrates functional conservation of the Wee1 mitotic inhibitor. Contrary to the dual-specificity kinase hypothesis, purified human Wee1 phosphorylates p34cdc2 exclusively on Tyr15 in vitro; no Thr14 phosphorylation was detected. Human and fission yeast Wee1 also specifically phosphorylate synthetic peptides at sites equivalent to Tyr15. Mutation of a critical lysine codon (Lys114) believed to be essential for kinase activity abolished both the in vivo mitotic inhibitor function and in vitro kinase activities of human Wee1. These results conclusively prove that Wee1 kinases inhibit mitosis by directly phosphorylating p34cdc2 on Tyr15, and strongly indicate that human cells have independent kinase pathways directing the two inhibitor phosphorylations of p34cdc2.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.