A5036314552- Cancer-related Molecular Pathways
- Cancer Mechanisms and Therapy
- Monoclonal and Polyclonal Antibodies Research
- Environmental law and policy
- Microtubule and mitosis dynamics
- Advanced Breast Cancer Therapies
- Melanoma and MAPK Pathways
- Ubiquitin and proteasome pathways
- HER2/EGFR in Cancer Research
- Glycosylation and Glycoproteins Research
- Mast cells and histamine
- DNA Repair Mechanisms
- Genomics and Chromatin Dynamics
- International Environmental Law and Policies
- Wnt/β-catenin signaling in development and cancer
- interferon and immune responses
- Virus-based gene therapy research
- Colorectal Cancer Treatments and Studies
- Legal principles and applications
- CAR-T cell therapy research
- Cancer Cells and Metastasis
- RNA Research and Splicing
- Drug-Induced Adverse Reactions
- Conflict of Laws and Jurisdiction
- Land Rights and Reforms
Bristol-Myers Squibb (United States)
2019-2024
The University of Sydney
1975-2024
University of Cambridge
2013-2024
European University Institute
2022
Novartis (United States)
2011-2021
Environmental Law Institute
2019
Novartis (Switzerland)
2016-2017
Novartis Institutes for BioMedical Research
2016-2017
Novartis Foundation
2015
Merck & Co., Inc., Rahway, NJ, USA (United States)
2010-2013
G1 cyclins control the to S phase transition in budding yeast, Saccharomyces cerevisiae. Cyclin E was discovered course of a screen for human complementary DNAs that rescue deficiency cyclin function yeast. The amounts both protein and an associated kinase activity fluctuated periodically through cell cycle; were maximal late early phases. E-associated correlated with appearance complexes containing cyclin-dependent Cdk2. Thus, E-Cdk2 complex may constitute G1-S phase-specific regulatory kinase.
The Raf family of protein kinases display differences in their abilities to promote the entry quiescent NIH 3T3 cells into S phase cell cycle. Although conditional activation deltaA-Raf:ER promoted cycle progression, deltaRaf-1:ER and deltaB-Raf:ER elicited a G1 arrest that was not overcome by exogenously added growth factors. Activation all three deltaRaf:ER led elevated expression cyclin D1 E reduced p27Kip1. However, induced p21Cip1, whereas did not. A catalytically potentiated form...
Cyclin-dependent kinases (CDK) are key positive regulators of cell cycle progression and attractive targets in oncology. SCH 727965 inhibits CDK2, CDK5, CDK1, CDK9 activity vitro with IC(50) values 1, 3, 4 nmol/L, respectively. was selected as a clinical candidate using functional screen vivo that integrated both efficacy safety parameters. Compared flavopiridol, exhibits superior an improved therapeutic index. In cell-based assays, completely suppressed retinoblastoma phosphorylation, which...
Cyclin E is classified as a putative G1 cyclin on the basis of its cyclic pattern mRNA expression, with maximal levels being detected near G1/S boundary. We report here that found associated transcription factor E2F in temporally regulated fashion. known to be critical for expression some S phase-specific proteins and thought important series others. Antisera specific were raised used demonstrate an association between E2F. This E/E2F complex was seen variety human cell lines from various...
Tumors put in a vulnerable position Cancer cells often display alterations metabolism that help fuel their growth. Such metabolic “rewiring” may also work against the cancer cells, however, by creating new vulnerabilities can be exploited therapeutically. A variety of human tumors show changes methionine caused loss gene coding for 5-methylthioadenosine phosphorylase (MTAP). Mavrakis et al. and Kryukov found MTAP renders cell lines sensitive to growth inhibition compounds suppress activity...
Cyclin-dependent kinases (Cdks) previously have been shown to drive the major cell cycle transitions in eukaryotic organisms ranging from yeast humans. We report here identification of a 28-kDa protein, p28Ick (inhibitor cyclin-dependent kinase), that binds and inhibits kinase activity preformed Cdk/cyclin complexes human cells. p28 inhibitory fluctuates during with maximal levels G1 accumulates G1- G0-arrested These results suggest control G1/S transition may be influenced by family Cdk...
Senescent human diploid fibroblasts are unable to enter S phase in response mitogenic stimulation. One of the key deficiencies mitogen-stimulated senescent cells is their failure phosphorylate retinoblastoma protein, which acts as an inhibitor entry into its unphosphorylated form. Recent data suggest that cyclin-dependent kinases (Cdks) regulated by G1 cyclins (D type and E) responsible for primary phosphorylation protein prior G1/S boundary. Surprisingly, we found 10- 15-fold higher...
We have isolated a human RNA polymerase II complex that contains chromatin structure remodeling activity and histone acetyltransferase activity. This the Srb proteins, Swi-Snf complex, acetyltransferases CBP PCAF in addition to II. Notably, general transcription factors are absent from this complex. The was purified by two different methods: conventional chromatography affinity using antibodies directed against CDK8, homolog of yeast Srb10 protein. Protein interaction studies demonstrate...
Inhibition of cyclin-dependent kinases (CDKs) has emerged as an attractive strategy for the development novel oncology therapeutics. Herein is described utilization in vivo screening approach with integrated efficacy and tolerability parameters to identify candidate CDK inhibitors a suitable balance activity tolerability. This resulted identification SCH 727965, potent selective inhibitor that currently undergoing clinical evaluation.
Background Hematopoietic progenitor kinase 1 (HPK1 or MAP4K1) has been demonstrated as a negative intracellular immune checkpoint in mediating antitumor immunity studies with HPK1 knockout and dead mice. Pharmacological inhibition of is desirable to investigate the role human cells therapeutic implications. However, significant challenge remains identify small molecule inhibitor sufficient potency, selectivity, other drug-like properties suitable for proof-of-concept studies. In this report,...
The U2 snRNP component SAP 155 contacts pre-mRNA on both sides of the branch site early in spliceosome assembly and is therefore positioned near or at catalytic center. We have isolated a cDNA encoding human identified its highly related Saccharomyces cerevisiae homolog (50% identity). carboxy-terminal two-thirds shows highest conservation remarkably similar to regulatory subunit A phosphatase PP2A. Significantly, phosphorylated concomitant with just after step one, making this first example...