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Bone age and factors affecting skeletal maturation at diagnosis of paediatric Cushing’s disease.pdf

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Bone age and factors affecting skeletal maturation at diagnosis of paediatric Cushing’s disease

Fréville et al. BMC Biology 2013, 11:80 /1741-7007/11/80 RESEARCH ARTICLE Open Access Plasmodium falciparum encodes a conserved active inhibitor-2 for Protein Phosphatase type 1: perspectives for novel anti-plasmodial therapy 1 2 1 1 1 1 Aline Fréville , Katia Cailliau-Maggio , Christine Pierrot , Géraldine Tellier , Hadidjatou Kalamou , Sophia Lafitte , 2 1 2 1* Alain Martoriati , Raymond J Pierce , Jean-François Bodart and Jamal Khalife Abstract Background: It is clear that the coordinated and reciprocal actions of kinases and phosphatases are fundamental in the regulation of development and growth of the malaria parasite. Protein Phosphatase type 1 is a key enzyme playing diverse and essential roles in cell survival. Its dephosphorylation activity/specificity is governed by the interaction of its catalytic subunit (PP1c) with regulatory proteins. Among these, inhibitor-2 (I2) is one of the most evolutionarily ancient PP1 regulators. In vivo studies in various organisms revealed a defect in chromosome segregation and cell cycle progression when the function of I2 is blocked. Results: In this report, we present evidence that Plasmodium falciparum, the causative agent of the most deadly form of malaria, expresses a structural homolog of mammalian I2, named PfI2. Biochemical, in vitro and in vivo studies revealed that PfI2 binds PP1 and inhibits its activity. We further showed that the motifs 12KTISW16 and 102HYNE105 are critical for PfI2 inhibitory activity. Functional studies using the Xenopus oocyte model revealed that PfI2 is able to overcome the G2/M cell cycle checkpoint by ind