Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.1.1.41 (isocitrate dehydrogenase)
 3,101 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cytokinins (CKs) are known to regulate leaf senescence and affect heat tolerance, but mechanisms underlying CK regulation of heat tolerance are not well understood. A comprehensive proteomic study was conducted to identify proteins altered by the expression of the adenine isopentenyl transferase (ipt) gene controlling CK synthesis and associated with heat tolerance in transgenic plants for a C(3) perennial grass species, Agrostis stolonifera. Transgenic plants with two different inducible promoters (SAG12 and HSP18) and a null transformant (NT) containing the vector without ipt were exposed to 20 degrees C (control) or 35 degrees C (heat stress) in growth chambers. Two-dimensional electrophoresis and mass spectrometry analysis were performed to identify protein changes in leaves and roots in response to ipt expression under heat stress. Transformation with ipt resulted in protein changes in leaves and roots involved in multiple functions, particularly in energy metabolism, protein destination and storage, and stress defence. The abundance levels of six leaf proteins (enolase, oxygen-evolving enhancer protein 2, putative oxygen-evolving complex, Rubisco small subunit, Hsp90, and glycolate oxidase) and nine root proteins (Fd-GOGAT, nucleotide-sugar dehydratase, NAD-dependent isocitrate dehydrogenase, ferredoxin-NADP reductase precursor, putative heterogeneous nuclear ribonucleoprotein A2, ascorbate peroxidase, dDTP-glucose 4-6-dehydratases-like protein, and two unknown proteins) were maintained or increased in at least one ipt transgenic line under heat stress. The diversity of proteins altered in transgenic plants in response to heat stress suggests a regulatory role for CKs in various metabolic pathways associated with heat tolerance in C(3) perennial grass species.
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PMID:Proteomic changes associated with expression of a gene (ipt) controlling cytokinin synthesis for improving heat tolerance in a perennial grass species. 2054 65

Small-molecule inhibitors of the phosphoinositide 3-kinase (PI3K), Akt, and mTOR pathway currently in the clinic produce a paradoxical reactivation of the pathway they are intended to suppress. Furthermore, fresh experimental evidence with PI3K antagonists in melanoma, glioblastoma, and prostate cancer shows that mitochondrial metabolism drives an elaborate process of tumor adaptation culminating with drug resistance and metastatic competency. This is centered on reprogramming of mitochondrial functions to promote improved cell survival and to fuel the machinery of cell motility and invasion. Key players in these responses are molecular chaperones of the Hsp90 family compartmentalized in mitochondria, which suppress apoptosis via phosphorylation of the pore component, Cyclophilin D, and enable the subcellular repositioning of active mitochondria to membrane protrusions implicated in cell motility. An inhibitor of mitochondrial Hsp90s in preclinical development (gamitrinib) prevents adaptive mitochondrial reprogramming and shows potent antitumor activity in vitro and in vivo. Other therapeutic strategies to target mitochondria for cancer therapy include small-molecule inhibitors of mutant isocitrate dehydrogenase (IDH) IDH1 (AG-120) and IDH2 (AG-221), which opened new therapeutic prospects for patients with high-risk acute myelogenous leukemia (AML). A second approach of mitochondrial therapeutics focuses on agents that elevate toxic ROS levels from a leaky electron transport chain; nevertheless, the clinical experience with these compounds, including a quinone derivative, ARQ 501, and a copper chelator, elesclomol (STA-4783) is limited. In light of this evidence, we discuss how best to target a resurgence of mitochondrial bioenergetics for cancer therapy.
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PMID:Molecular Pathways: Mitochondrial Reprogramming in Tumor Progression and Therapy. 2666 May 17