A5102724497- PI3K/AKT/mTOR signaling in cancer
- Melanoma and MAPK Pathways
- Phytase and its Applications
- RNA Research and Splicing
- Free Radicals and Antioxidants
- Protein Kinase Regulation and GTPase Signaling
- Computational Drug Discovery Methods
- Cell death mechanisms and regulation
- Polyamine Metabolism and Applications
- Cancer, Hypoxia, and Metabolism
- Eicosanoids and Hypertension Pharmacology
- Synthesis and biological activity
- Cell Adhesion Molecules Research
- DNA Repair Mechanisms
- Cancer Cells and Metastasis
- Cancer-related Molecular Pathways
- Cellular transport and secretion
- Fungal and yeast genetics research
- Autophagy in Disease and Therapy
- PARP inhibition in cancer therapy
- Pancreatic function and diabetes
- Protein Degradation and Inhibitors
- Microtubule and mitosis dynamics
- Peptidase Inhibition and Analysis
- Erythrocyte Function and Pathophysiology
University of Illinois Chicago
2019-2023
Illinois College
2018-2023
Weill Cornell Medicine
2016-2019
Cornell University
2015-2019
University of Illinois Urbana-Champaign
2018-2019
Harvard University
2005-2015
Institute for Research in Immunology and Cancer
2013
University of Cincinnati
2011-2013
Université de Montréal
2013
University of Cincinnati Medical Center
2011-2013
Survivin, an apoptosis inhibitor/cell-cycle regulator, is critically required for suppression of and ensuring normal cell division in the G2/M phase cycle. It highly expressed a cycle-regulated manner localizes together with caspase-3 on microtubules within centrosomes. Whether survivin physiologically relevant caspase inhibitor has been unclear due to difficulties obtaining correctly folded finding right conditions inhibition assay. In this study, recombinant, active human was Escherichia...
Hyperactivation of Ras-ERK1/2 signaling is critical to the development many human malignancies, but little known regarding specific contribution ERK1 or ERK2 oncogenic processes. We demonstrate that not necessary for Ras-induced epithelial-to-mesenchymal transformation (EMT). Further, overexpression sufficient induce EMT. Many ERK1/2-interacting proteins contain amino acid motifs, e.g., DEF D-motifs, which regulate docking with ERK1/2. Remarkably, motif-containing targets required EMT and...
Abstract Hypoxia plays a key role in tumor cell survival, invasion, and metastasis. Here we show that hypoxia increases invasion by the modulation of Rab11, an important molecule for vesicular trafficking, especially membrane protein recycling translocation proteins from trans-Golgi network to plasma membrane. Dominant-negative Rab11 dramatically decreased hypoxia-induced MDA-MB-231 breast carcinoma cells without affecting apoptosis. Hypoxia-induced trafficking is regulated microtubule...
The p70 ribosomal protein S6 kinase 1 (S6K1) plays a key role in cell growth and proliferation by regulating insulin sensitivity, metabolism, synthesis, cycle. Thus, deregulation of S6K contributes to the progression type 2 diabetes, obesity, aging, cancer. Considering biological clinical importance S6K1, complete understanding its regulation is critical. One motifs activation S6K1 turn motif, but not well understood. Here we provide evidence for two mechanisms modulating motif...
Highlights•Low glucose induces ER stress, resulting in PERK/Akt activation and cell survival•Sustained metabolic stress promotes isoform-specific MEK1/ERK2-dependent death•ERK2 apoptosis through ATF4-dependent Bid, cFos, Trb3 expression•Low-glucose-induced death is prevented by supplementation of glutamateSummaryInsufficient nutrients disrupt physiological homeostasis, diseases even death. Considering the pathological consequences this adaptive responses that cells utilize under condition...
Abstract Matrix metalloproteinase (MMP)-9 plays a key role in tumor invasion. Inhibitors of MMP-9 were screened from Metasequoia glyptostroboides (Dawn redwood) and one potent inhibitor, isoginkgetin, biflavonoid, was identified. Noncytotoxic levels isoginkgetin decreased production profoundly, but up-regulated the level tissue inhibitor (TIMP)-1, an MMP-9, HT1080 human fibrosarcoma cells. The major mechanism Ras-dependent cells phosphatidylinositol 3-kinase (PI3K)/Akt/nuclear factor-κB...
ERK is a key coordinator of the epithelial-to-mesenchymal transition (EMT) in that variety EMT-inducing factors activate signaling pathways converge on to regulate EMT transcription programs. However, mechanisms by which controls program are not well understood. Through an analysis global changes gene expression mediated ERK2, we identified factor FoxO1 as potential mediator ERK2-induced EMT, and thus investigated mechanism ERK2 regulates FoxO1. Additionally, our revealed induced Dock10,...
Metabolic reprogramming is a hallmark of cancer that includes increased glucose uptake and accelerated aerobic glycolysis. This phenotype required to fulfill anabolic demands associated with aberrant cell proliferation often mediated by oncogenic drivers such as activated BRAF. In this study, we show the MAPK-activated p90 ribosomal S6 kinase (RSK) necessary maintain glycolytic metabolism in BRAF-mutated melanoma cells. RSK directly phosphorylated regulatory domain...
Cells maintain and dynamically change their proteomes according to the environment needs. Mechanistic target of rapamycin (mTOR) is a key regulator proteostasis, homeostasis proteome. Thus, dysregulation mTOR leads changes in proteostasis consequent progression diseases, including cancer. Based on physiological clinical importance signaling, we investigated feedback cell fate. Here, reveal that targeting inhibits eIF4E-mediated cap-dependent translation, but signaling activates translation...
Abstract ErbB2 (HER2, Neu) and Ras play key roles in tumor invasion metastasis. We identified a novel mechanism by which integrin α6β4 regulates expression, activation, the of breast carcinoma cells. Here we show that activity especially serum-depleted condition. Down-regulation β4 short hairpin RNA (shRNA) decreased whereas reexpression this restored activity. ErbB2, binding partner epidermal growth factor receptor (EGFR), EGFR modulated activity, regulated phospho-EGFR level without...
Deregulation of translation initiation factors contributes to many pathogenic conditions, including cancer. Here, we report the definition a novel regulatory pathway for translational with possible therapeutic import in Specifically, found that casein kinase 1ε (CK1ε) is highly expressed breast tumors and plays critical role cancer cell proliferation by controlling mRNA translation. Eukaryotic factor eIF4E, an essential component complex eIF4F, downregulated binding negative-acting 4E-BP1....
Amidase signature family enzymes, which are widespread in nature, contain a newly identified Ser-cisSer-Lys catalytic triad the peptide bond between Ser131 and preceding residue Gly130 is cis configuration. In order to characterize property of novel triad, we have determined structures five mutant malonamidase E2 enzymes that Cys-cisSer-Lys, Ser-cisAla-Lys, or Ser-cisSer-Ala substitution with alanine. Cysteine cannot replace role Ser155 due hyper-reactivity residue, results modification...
mTORC1 is a central signaling node in controlling cell growth, proliferation, and metabolism that aberrantly activated cancers certain cancer-associated genetic disorders, such as tuberous sclerosis complex (TSC) sporadic lymphangioleiomyomatosis. However, while mTORC1-inhibitory compounds (rapamycin rapalogs) attracted interest candidate therapeutics, clinical trials have not replicated the promising findings preclinical models, perhaps because these tend to limit proliferation without...
Integrins are major mediators of cancer cell adhesion to extracellular matrix. Through this interaction, integrins play critical roles in migration, invasion, metastasis, and resistance apoptosis during tumor progression. Recent studies highlight the importance integrin trafficking, endocytosis recycling, for functions cells. Understanding molecular mechanisms trafficking is pivotal understanding progression development anticancer drugs.
The polypyrimidine tract-binding protein (PTB), an RNA-binding protein, is required for efficient translation of some mRNAs containing internal ribosomal entry sites (IRESs). Here we provide evidence that the addition apoptosis-inducing agents to cells results in cleavage PTB isoforms 1, 2, and 4 by caspase-3. This separated N-terminal region, NLS-RRM1, from C-terminal RRM2-3-4. Our data indicate there are three noncanonical caspase-3 target PTBs, namely Ile-Val-Pro-Asp<sup>7</sup>↓Ile,...
Abstract Active Ras proteins contribute to breast carcinogenesis and progression. Here, we provide evidence that active H-Ras regulates the expression activity of E2F family transcription factors in SUM-159 carcinoma cells. In addition, show by using a DNA-binding mutant E2F, as well specific E2Fs are transcriptionally active, E2Fs1-3 can mediate H-Ras-dependent invasion The inhibitory E2Fs4-5, contrast, do not influence invasion. One mechanism which promote seems be their ability increase...
In the fission yeast Schizosaccharomyces pombe, septation and constriction of actomyosin ring for cell division are positively regulated by Spg1 GTPase, a member Ras superfamily. is negatively Byr4 Cdc16, which together form two-component GTPase-activating protein GTPase. To better understand how regulates septation, mutants were tested in vitro functions. This analysis revealed that contained one Cdc16-binding site four Spg1-binding sites (SBS), designated SBS1–SBS4. Although with single...
Vascular morphogenesis is a key process for development, reproduction, and pathogenesis. Thus understanding the mechanisms of this pathophysiological importance. Despite fact that collagen I most abundant potent promorphogenic molecule known, molecular by which protein regulates endothelial cell tube are still unclear. Here we provide strong evidence induces inhibiting glycogen synthase kinase 3β (GSK3β). Further mechanistic studies revealed GSK3β activity regulated D (PKD). PKD inhibited...