A5060825857- Heat shock proteins research
- ATP Synthase and ATPases Research
- Endoplasmic Reticulum Stress and Disease
- Genetics, Aging, and Longevity in Model Organisms
- Cancer, Hypoxia, and Metabolism
- Connexins and lens biology
- Peptidase Inhibition and Analysis
- Metabolism, Diabetes, and Cancer
- Glutathione Transferases and Polymorphisms
- Protease and Inhibitor Mechanisms
- Genomics, phytochemicals, and oxidative stress
- Muscle metabolism and nutrition
- Enzyme Structure and Function
- Protein Tyrosine Phosphatases
- Cell Adhesion Molecules Research
- thermodynamics and calorimetric analyses
- Biochemical and Molecular Research
SUNY Upstate Medical University
2017-2021
Highlights•Stress-inducible TIMP2 is a bona fide co-chaperone of extracellular HSP90 (eHSP90)•TIMP2 regulates chaperone function and interaction with client MMP2•Secreted co-chaperones AHA1 displace each other on the eHSP90:MMP2 complex•TIMP2-AHA1 competition impacts MMP2 activity matrix gelatinolysisSummaryThe molecular heat shock protein 90 (eHSP90) stabilizes protease metalloproteinase 2 (MMP2), leading to tumor cell invasion. Although are critical modulators intracellular HSP90:client...
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...
The serine/threonine protein phosphatase 5 (PP5) regulates multiple cellular signaling networks. A number of factors, including heat shock 90 (Hsp90), promote the activation PP5. However, it is unclear whether post-translational modifications also influence PP5 activity. Here, we show an "on/off switch" mechanism for regulation. casein kinase 1δ (CK1δ) phosphorylates T362 in catalytic domain PP5, which activates and enhances activity independent Hsp90. Overexpression phosphomimetic T362E-PP5...
The tissue inhibitor of metalloproteinases 2 (TIMP-2) is a specific endogenous matrix metalloproteinase (MMP-2), which key enzyme that degrades the extracellular and promotes tumor cell invasion. Although TIMP-2:MMP-2 complex controls proteolysis, signaling mechanism by two proteins associate in space remains unidentified. Here we report TIMP-2 phosphorylated outside secreted c-Src tyrosine kinase. As consequence, phosphorylation at Y90 significantly enhances potency as an MMP-2 weakens...
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...
You have accessJournal of UrologyKidney Cancer: Basic Research & Pathophysiology I1 Apr 2018PD46-11 PHOSPHORYLATION AND UBIQUITINATION REGULATE PROTEIN PHOSPHATASE-5 ACTIVITY ITS PROSURVIVAL ROLE IN KIDNEY CANCER Natela Dushukyan, Michael Daneshvar, Rebecca Sager, Mark Woodford, Alexander Baker-Williams, John Chisholm, David Loiselle, Andrew Truman, Timothy Haystead, Oleg Shapiro, Dimitra Bourboulia, Gennady Bratslavsky, and Mehdi Mollapour DushukyanNatela Dushukyan More articles by this...