Dynamic Regulation of Tgf-B Signaling by Tif1γ: A Computational Approach

TIF1γ (Transcriptional Intermediary Factor 1 γ) has been implicated in Smad-dependent signaling by Transforming Growth Factor beta (TGF-β). Paradoxically, TIF1γ functions both as a transcriptional repressor or as an alternative transcription factor that promotes TGF-β signaling. Using ordinary differential-equation models, we have investigated the effect of TIF1γ on the dynamics of TGF-β signaling. An integrative model that includes the formation of transient TIF1γ-Smad2-Smad4 ternary complexes is the only one that can account for TGF-β signaling compatible with the different observations reported for TIF1γ. In addition, our model predicts that varying TIF1γ/Smad4 ratios play a critical role in the modulation of the transcriptional signal induced by TGF-β, especially for short stimulation times that mediate higher threshold responses. Chromatin immunoprecipitation analyses and quantification of the expression of TGF-β target genes as a function TIF1γ/Smad4 ratios fully validate this hypothesis. Our integrative model, which successfully unifies the seemingly opposite roles of TIF1γ, also reveals how changing TIF1γ/Smad4 ratios affect the cellular response to stimulation by TGF-β, accounting for a highly graded determination of cell fate

A single injection of compound 6 evoked an LH surge and ovulation in 18 week old gilts

International audienc

Rotaxanes of cyclic peptides

The synthesis of rotaxanes derived from the synthetic peptide macrocycles cyclo(l-ProGly)4 and cyclo(l-ProGly)5 and diammonium threads is described. [2]Rotaxanes are formed in good yields (56−63%), despite the disruption of internal amide−amide hydrogen bonding in the macrocycles

La kisspeptine : une nouvelle voie pour maitriser l’ovulation chez les petits ruminants ?

National audienceLa découverte de la kisspeptine (KP) à été une avancée majeur pour comprendre les mécanismes qui sous-tendent le contrôle central de la reproduction. Plusieurs formes de la KP (KP54, KP16, KP14, KP13 et KP10), toutes dérivées de la forme la plus longue (KP54) ont été détectées dans le cerveau et sont toutes capables d’activer le même récepteur (KISS1R), mais la forme la plus étudiées est la KP10 (H-YNWNSFGLRY-NH 2 ). Chez les mammifères l’injection périphérique de la KP10 induit une augmentation de la sécrétion de la GnRH (gonadotropin releasing hormone) suivie par une augmentation de la concentration plasmatique de la LH. Nous avons démontré qu’une infusion continue de la KP10 pendent l’anoestrus est capable de réactiver l’axe hypothalamo-hypophyse-gonade et d’induire une ovulation

Native Chemical ligation simplifies the access of multi-domain antimicrobial peptides: application to the study of big-defensins

International audienc

Protected maleimide building blocks for the decoration of peptides, peptoids and peptide nucleic acids

Monomers allowing for the introduction of [2,5-dimethylfuran]-protected maleimides into polyamides such as peptides, peptide nucleic acids, and peptoids were prepared, as well as the corresponding oligomers. Suitable maleimide deprotection conditions were established in each case. The stability of the adducts generated by Michael-type maleimide-thiol reaction and Diels-Alder cycloaddition to maleimide deprotection conditions was exploited to prepare a variety of conjugates from peptide and PNA scaffolds incorporating one free and one protected maleimide. The target molecules were synthesized by using two subsequent maleimide-involving click reactions separated by a maleimide deprotection step. Carrying out maleimide deprotection and conjugation simultaneously gave better results than performing the two reactions subsequently