A5084025867- Cancer-related Molecular Pathways
- Ubiquitin and proteasome pathways
- Cancer-related gene regulation
- Enzyme Structure and Function
- Genetics, Aging, and Longevity in Model Organisms
- Signaling Pathways in Disease
- Genetics and Neurodevelopmental Disorders
- Ovarian cancer diagnosis and treatment
- Autophagy in Disease and Therapy
- CRISPR and Genetic Engineering
- S100 Proteins and Annexins
- Heat shock proteins research
- Monoclonal and Polyclonal Antibodies Research
- Multiple and Secondary Primary Cancers
- Protease and Inhibitor Mechanisms
- Epigenetics and DNA Methylation
- Glycosylation and Glycoproteins Research
- Cancer, Hypoxia, and Metabolism
- Muscle Physiology and Disorders
- Cellular Mechanics and Interactions
- Renal cell carcinoma treatment
- DNA Repair Mechanisms
- Peptidase Inhibition and Analysis
- Genetic Neurodegenerative Diseases
- Endoplasmic Reticulum Stress and Disease
Newcastle University
2017-2024
University of Liverpool
2011-2012
Polish Academy of Sciences
2009
Selective recruitment of protein kinases to the Hsp90 system is mediated by adaptor co-chaperone Cdc37. We show that assembly CDK4 and CDK6 into complexes differentially regulated Cdc37-Hsp90 system. Like other kinase clients, binding CDK4/6 Cdc37 blocked ATP-competitive inhibitors. relinquishes D3- virus-type cyclins INK family CDK inhibitors, whereas relinquished INKs but less readily cyclins. p21CIP1 p27KIP1 inhibitors are potent than at displacing from However, they cooperate with D-type...
Filament assembly of nonmuscle myosin IIA (NMIIA) is selectively regulated by the small Ca2+-binding protein, S100A4, which causes enhanced cell migration and metastasis in certain cancers. Our NMR structure shows that an S100A4 dimer binds to a single heavy chain asymmetrical configuration. NMIIA complex forms continuous helix stretches across surface engages Ca2+-dependent binding sites each subunit dimer. Synergy between these leads very tight association (KD ∼1 nM) unique S100 family....
USP15 and bind by X-ray crystallography ( View interaction ) The post-translational modification of proteins ubiquitin, catalysed E3 ligases, is critical for many aspects cellular function may affect the targeted through alterations in stability, localisation or activity [1]. Ubiquitination reversible since isopeptide bonds within ubiquitin chains between its conjugated substrate can be hydrolysed deubiquitinating enzymes (DUBs). human genome encodes approximately 90 DUBs [2-4] from five...
The SCFSKP2 ubiquitin ligase relieves G1 checkpoint control of CDK-cyclin complexes by promoting p27KIP1 degradation. We describe reconstitution stable containing SKP1-SKP2 and CDK1-cyclin B or CDK2-cyclin A/E, mediated the CDK regulatory subunit CKS1. further show that a direct interaction between SKP2 N-terminal motif cyclin A can stabilize SKP1-SKP2-CDK2-cyclin in absence identify binding site on demonstrate is not present E. This distinct from but overlapping with features mediate other...
Abstract The SCF SKP2 ubiquitin ligase relieves G1 checkpoint control of CDK-cyclin complexes by promoting p27KIP1 degradation. We describe reconstitution stable containing SKP1-SKP2 and CDK1-cyclin B or CDK2-cyclin A/E, mediated the CDK regulatory subunit CKS1. further show that a direct interaction between N-terminal motif cyclin A can stabilize SKP1-SKP2-CDK2-cyclin in absence identify binding site on demonstrate is not present E. This distinct from but overlapping with features mediate...
We describe the generation and characterization of camelid single-domain antibodies (nanobodies) raised against tumor suppressor protein p16INK4a (p16). p16 plays a critical role in cell cycle by inhibiting cyclin-dependent kinases CDK4 CDK6, it is inactivated sporadic familial cancers. The majority missense mutations cause loss function destabilizing structure. show that nanobodies bind with nanomolar affinities restore stability range different cancer-associated located at sites throughout...