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Genipin inhibits UCP2-mediated proton leak and acutely reverses obesity- and high glucose-induced beta cell dysfunction in isolated pancreatic islets.
RNA G-quadruplexes cause eIF4A-dependent oncogene translation in cancer
An eIF4A RNA helicase-dependent mechanism of translational control that contributes to oncogenesis and underlies the anticancer effects of silvestrol and related compounds is reported.
Antitumor Activity and Mechanism of Action of the Cyclopenta[b]benzofuran, Silvestrol
The results indicate that silvestrol is a potent anti-cancer compound in vivo that exerts its activity by affecting survival pathways as well as angiogenesis, and it is proposed thatsilvestrol mediates its effects by preferentially inhibiting translation of malignancy-related mRNAs.
Tight Coordination of Protein Translation and HSF1 Activation Supports the Anabolic Malignant State
The ribosome functions as a central information hub in malignant cells: Translational flux conveys information about the cell’s metabolic status to regulate the transcriptional programs that support it, and multiple unbiased chemical and genetic approaches establish HSF1 as a prime transducer of this information.
nanoCAGE reveals 5' UTR features that define specific modes of translation of functionally related MTOR-sensitive mRNAs.
5' UTR features define different modes ofMTOR-sensitive translation of functionally distinct subsets of mRNAs, which may explain the diverse impact of MTOR and EIF4A inhibitors on neoplastic cells.
Targeting heat shock response to sensitize cancer cells to proteasome and Hsp90 inhibitors.
- Nava Zaarur, V. Gabai, J. Porco, S. Calderwood, M. Sherman
- Biology, ChemistryCancer research
- 1 February 2006
This work knocked out the major heat shock transcription factor HSF-1 in several cancer cell lines using small interfering RNA and showed that such cells, which can no longer induce Hsps in response to proteasome and Hsp90 inhibitors, become more sensitive to these drugs.
Therapeutic suppression of translation initiation modulates chemosensitivity in a mouse lymphoma model.
- Marie-Ève Bordeleau, F. Robert, J. Pelletier
- Biology, ChemistryThe Journal of clinical investigation
- 1 July 2008
It is established that targeting translation initiation can restore drug sensitivity in vivo and provide an approach to modulating chemosensitivity.
Inhibition of transcription factor NF-kappaB signaling proteins IKKbeta and p65 through specific cysteine residues by epoxyquinone A monomer: correlation with its anti-cancer cell growth activity.
Pestacin: a 1,3-dihydro isobenzofuran from Pestalotiopsis microspora possessing antioxidant and antimycotic activities
How Proteins Bind Macrocycles
Analysis of the binding modes of a representative set of macrocycle-protein complexes provides evidence that large, natural product derived macrocycles can bind to targets that are not druggable by conventional, drug-like compounds, supporting the notion that natural product inspired synthetic macro cycles can expand the number of proteins that are druggability by synthetic small molecules.