A5014299665- Heat shock proteins research
- ATP Synthase and ATPases Research
- Endoplasmic Reticulum Stress and Disease
- Enzyme Structure and Function
- Protein Tyrosine Phosphatases
- Ubiquitin and proteasome pathways
- Renal cell carcinoma treatment
- Cancer, Hypoxia, and Metabolism
- Autophagy in Disease and Therapy
- Metabolism, Diabetes, and Cancer
- Plant biochemistry and biosynthesis
- Ferroptosis and cancer prognosis
- RNA Research and Splicing
- Computational Drug Discovery Methods
- Galectins and Cancer Biology
- Advanced Breast Cancer Therapies
- Glutathione Transferases and Polymorphisms
- Protease and Inhibitor Mechanisms
- DNA Repair Mechanisms
- Glycosylation and Glycoproteins Research
- Renal and related cancers
- Tuberous Sclerosis Complex Research
- Effects of Radiation Exposure
- Biochemical and Molecular Research
- Genomics, phytochemicals, and oxidative stress
SUNY Upstate Medical University
2019-2024
State University of New York
2023
Upstate University Hospital
2022
Abstract Protein folding quality control in cells requires the activity of a class proteins known as molecular chaperones. Heat shock protein‐90 (Hsp90), multidomain ATP driven machine, is prime representative this family proteins. Interactions between Hsp90, its co‐chaperones, and client have been shown to be important facilitating correct activation clients. Hsp90 levels functions are elevated tumor cells. Here, we computationally predict regions on native structures clients c‐Abl, c‐Src,...
Highlights•Casein-kinase-2-mediated sequential phosphorylation of the co-chaperone FNIP1•FNIP1 relay leads to gradual activation Hsp90 clients•Serine/threonine protein phosphatase 5 (PP5) dephosphorylates FNIP1•O-GlcNAcylation causes ubiquitination and proteasomal degradation FNIP1SummaryThe molecular chaperone stabilizes activates client proteins. Co-chaperones post-translational modifications tightly regulate function consequently lead clients. However, it is unclear whether this process...
Dysregulated metabolism is one of the hallmarks cancer. Under normal physiological conditions, ATP primarily generated by oxidative phosphorylation. Cancers commonly undergo a dramatic shift toward glycolysis, despite presence oxygen. This phenomenon known as Warburg effect, and requires activity LDHA. LDHA converts pyruvate to lactate in final step glycolysis often upregulated inhibitors present promising therapeutic option, blockade leads apoptosis cancer cells. Despite this, existing have...
Heat shock protein-90 (Hsp90) chaperone machinery is involved in the stability and activity of its client proteins. The function Hsp90 regulated by co-chaperones post-translational modifications. Although structural evidence exists for interaction with clients, our understanding impact toward cells remains elusive. Here, we dissect recently identified higher eukaryotic co-chaperones, FNIP1/2 (FNIPs) Tsc1, activity. Our data show that Tsc1 FNIP2 form mutually exclusive complexes FNIP1, unlike...
Cellular homeostasis relies on both the chaperoning of proteins and intracellular degradation system that delivers cytoplasmic constituents to lysosome, a process known as autophagy. The crosstalk between these processes their underlying regulatory mechanisms is poorly understood. Here, we show molecular chaperone heat shock protein 90 (Hsp90) forms complex with autophagy-initiating kinase Atg1 (yeast)/Ulk1 (mammalian), which suppresses its activity. Conversely, environmental cues lead...
Proteostasis, the maintenance of proper protein folding, stability, and degradation within cells, is fundamental for cellular function. Two key players in this intricate process are macroautophagy/autophagy chaperoning nascent proteins. Here, we explore crosstalk between autophagy HSP90 chaperone maintaining proteostasis, highlighting their interplay significance homeostasis.
c-Src tyrosine kinase is a renowned key intracellular signaling molecule and potential target for cancer therapy. Secreted recent observation, but how it contributes to extracellular phosphorylation remains elusive. Using series of domain deletion mutants, we show that the N-proximal region essential its secretion. The tissue inhibitor metalloproteinases 2 (TIMP2) an substrate c-Src. Limited proteolysis-coupled mass spectrometry mutagenesis studies verify Src homology 3 (SH3) P31VHP34 motif...
The molecular chaperone Heat shock protein 90 (Hsp90) is essential for the folding, stability, and activity of several drivers oncogenesis. Hsp90 inhibitors are currently under clinical evaluation cancer treatment, however their efficacy limited by lack biomarkers to optimize patient selection. We have recently identified tumor suppressor tuberous sclerosis complex 1 (Tsc1) as a new co-chaperone that affects binding its inhibitors. Highly variable mutations TSC1 been previously in bladder...
The 2nd International Symposium on the Chaperone Code took place October 26-28, 2023 at Hilton Alexandria Old Town, VA, USA. event featured more than 100 attendees from ten countries and provided a dynamic platform for established researchers, emerging investigators, postdoctoral fellows, students to share insights ideas diverse facets of molecular chaperones with strong focus their regulation by post-translational modifications. format fostered discussions collaboration among participants....
The serine/threonine protein phosphatase 5 (PP5) regulates hormone and stress-induced signaling networks. Unlike other phosphoprotein phosphatases, PP5 contains both regulatory catalytic domains is further regulated through post-translational modifications (PTMs). Here we identify that SUMOylation of K430 in the domain activity. Additionally, phosphorylation PP5-T362 pre-requisite for SUMOylation, suggesting ordered addition PTMs function cells. Using glucocorticoid receptor, a well known...
The molecular chaperone TNF-receptor-associated protein-1 (TRAP1) controls mitochondrial respiration through regulation of Krebs cycle and electron transport chain activity. Post-translational modification (PTM) TRAP1 regulates its activity, thereby controlling global metabolic flux. O-GlcNAcylation is one PTM that known to impact metabolism, however the major effectors this regulatory remain inadequately resolved. Here we demonstrate TRAP1-O-GlcNAcylation decreases ATPase leading increased...
Heat shock protein-90 (Hsp90) is an essential molecular chaperone in eukaryotes that plays a vital role protecting and maintaining the functional integrity of deregulated signaling proteins tumors. We have previously reported stability activity mitotic checkpoint kinase Mps1 depend on Hsp90. In turn, Mps1-mediated phosphorylation Hsp90 regulates its function for arrest. Cdc14-assisted dephosphorylation exit. Post-translational regulation also known as "Chaperone Code." Here, we demonstrate...