A5073156412- Microtubule and mitosis dynamics
- Cancer-related Molecular Pathways
- Ubiquitin and proteasome pathways
- Cancer Cells and Metastasis
- Cancer Genomics and Diagnostics
- RNA modifications and cancer
- DNA Repair Mechanisms
- Cancer Research and Treatments
- Cancer, Hypoxia, and Metabolism
- Breast Cancer Treatment Studies
- Peptidase Inhibition and Analysis
- 14-3-3 protein interactions
- Lung Cancer Treatments and Mutations
- Lung Cancer Research Studies
- Virus-based gene therapy research
- Viral Infectious Diseases and Gene Expression in Insects
- Protein Degradation and Inhibitors
- Advanced Breast Cancer Therapies
- Pancreatic and Hepatic Oncology Research
- Cancer Treatment and Pharmacology
- Epigenetics and DNA Methylation
- PARP inhibition in cancer therapy
- Protein Kinase Regulation and GTPase Signaling
- Protein Tyrosine Phosphatases
- International Arbitration and Investment Law
The University of Texas MD Anderson Cancer Center
2015-2024
The University of Texas Health Science Center at Houston
2018-2024
Washington University in St. Louis
2004-2018
Mallinckrodt (United States)
2002-2013
Imaging Center
2002-2013
Centre for Cancer Biology
1991-2012
Alvin J. Siteman Cancer Center
2010-2012
University of Missouri–St. Louis
2012
Howard Hughes Medical Institute
2002-2011
Lymphatic Education & Research Network
2008
Human Cdc25C is a dual-specificity protein phosphatase that controls entry into mitosis by dephosphorylating the kinase Cdc2. Throughout interphase, but not in mitosis, was phosphorylated on serine-216 and bound to members of highly conserved ubiquitously expressed family 14-3-3 proteins. A mutation preventing phosphorylation abrogated binding. Conditional overexpression this mutant perturbed mitotic timing allowed cells escape G 2 checkpoint arrest induced either unreplicated DNA or...
In response to DNA damage, mammalian cells prevent cell cycle progression through the control of critical regulators. A human gene was identified that encodes protein Chk1, a homolog Schizosaccharomyces pombe Chk1 kinase, which is required for damage checkpoint. Human modified in damage. vitro bound and phosphorylated dual-specificity phosphatases Cdc25A, Cdc25B, Cdc25C, transitions by dephosphorylating cyclin-dependent kinases. phosphorylates Cdc25C on serine-216. As shown an accompanying...
Chk1 is an evolutionarily conserved protein kinase that regulates cell cycle progression in response to checkpoint activation.In this study, we demonstrated agents block DNA replication or cause certain forms of damage induce the phosphorylation human Chk1.The phosphorylated form possessed higher intrinsic activity and eluted more quickly on gel filtration columns.Serines 317 345 were identified as sites vivo, ATR (the ATM-and Rad3-related kinase) both these vitro.Furthermore, serines vivo...
To correlate the variable clinical features of oestrogen-receptor-positive breast cancer with somatic alterations, we studied pretreatment tumour biopsies accrued from patients in two studies neoadjuvant aromatase inhibitor therapy by massively parallel sequencing and analysis. Eighteen significantly mutated genes were identified, including five (RUNX1, CBFB, MYH9, MLL3 SF3B1) previously linked to haematopoietic disorders. Mutant MAP3K1 was associated luminal A status, low-grade histology...
Entry into mitosis in Schizosaccharomyces pombe is negatively regulated by the wee1+ gene, which encodes a protein kinase with serine-, theonine-, and tyrosine-phosphorylating activities. The regulates phosphorylating p34cdc2 on tyrosine 15, thereby inactivating p34cdc2-cyclin B complex. human homolog of gene (WEE1Hu) was overproduced bacteria assayed an vitro system. Unlike its fission yeast homolog, product WEE1Hu encoded tyrosine-specific kinase. WEE1 phosphorylated complex 15 but not...
A checkpoint operating in the G<sub>2</sub> phase of cell cycle prevents entry into mitosis presence DNA damage. UCN-01, a protein kinase inhibitor currently undergoing clinical trials for cancer treatment, abrogates function and sensitizes p53-defective cells to DNA-damaging agents. In most species, Cdc25 phosphatase from removing inhibitory phosphate groups mitosis-promoting Cdc2. This is accomplished by maintaining phosphorylated form that binds 14-3-3 proteins. The kinases, Chk1 Cds1,...
We have shown earlier that certain proline-directed kinases such as MAP kinase or GSK-3 can phosphorylate tau protein in an abnormal manner reminiscent of from Alzheimer paired helical filaments [Drewes et al. (1992); Mandelkow (1992)]. Both are abundant brain tissue and associate physically with microtubules through several cycles assembly disassembly. In this report we show cdk2/cyclin A incorporates = 5 Pi into recombinant tau, it also induces the MR shift antibody reactivity typical tau....
Checkpoint kinase (Chk)1 is an evolutionarily conserved protein that was first identified in fission yeast as essential component of the DNA damage checkpoint. In mice, Chk1 provides function absence environmentally imposed genotoxic stress. Here we show human cells lacking exhibit defects both ionizing radiation (IR)-induced S and G 2 checkpoints. addition, loss resulted accumulation a hypophosphorylated form Cdc25A phosphatase, Chk1-deficient failed to degrade after IR. The IR-induced...
Signaling pathways regulating proliferation, differentiation, and apoptosis are commonly mediated through protein–protein interactions as well reversible phosphorylation of proteins. To facilitate the study regulated in cells living animals, we optimized firefly luciferase protein fragment complementation by screening incremental truncation libraries N- C-terminal fragments luciferase. Fused to rapamycin-binding domain (FRB) kinase mammalian target rapamycin FK506-binding 12 (FKBP),...
Resistance to neoadjuvant chemotherapy in triple-negative breast cancer can be mediated by a reversible chemotherapy-tolerant state.
Patients with triple-negative breast cancer (TNBC) - defined by lack of estrogen receptor and progesterone expression as well human epidermal growth factor 2 (HER2) amplification have a poor prognosis. There is need for targeted therapies to treat this condition. TNBCs frequently harbor mutations in TP53, resulting loss the G1 checkpoint reliance on kinase 1 (Chk1) arrest cells response DNA damage. Previous studies shown that inhibition Chk1 p53-deficient background results apoptosis...
Effective targeted therapies for small-cell lung cancer (SCLC), the most aggressive form of cancer, remain urgently needed. Here we report evidence preclinical efficacy evoked by targeting overexpressed cell-cycle checkpoint kinase CHK1 in SCLC. Our studies employed RNAi-mediated attenuation or pharmacologic blockade with novel second-generation inhibitor prexasertib (LY2606368), currently clinical trials. In SCLC models vitro and vivo, LY2606368 exhibited strong single-agent efficacy,...
Talazoparib has demonstrated efficacy in patients with BRCA-positive metastatic breast cancer. This study evaluated the pathologic response of talazoparib alone for 6 months a known germline BRCA pathogenic variant (gBRCA-positive) and operable cancer.Eligibility included 1 cm or larger invasive tumor gBRCA-positive disease. Human epidermal growth factor receptor 2-positive tumors were excluded. Twenty underwent pretreatment biopsy, once per day oral (1 mg), followed by definitive surgery....
Entry into mitosis requires the activity of Cdc2 kinase. associates with B-type cyclins, and Cdc2-cyclin B heterodimer is in turn regulated by phosphorylation. Phosphorylation threonine 161 required for complex to be catalytically active, whereas phosphorylation 14 tyrosine 15 inhibitory. Human kinases that catalyze have been identified. Here we report isolation a novel human cDNA encoding dual-specificity protein kinase (designated Myt1Hu) preferentially phosphorylates on cyclin-dependent...