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821.
The dynamic behaviour of an open futile cycle composed of two enzymes has been investigated in the vicinity of a steady-state. A necessary condition required for damped or sustained oscillations of the system is that enzyme E2, which controls recycling of the substrate S2, be inhibited by an excess of this substrate. In order for the system to be neutrally stable and therefore to exhibit sustained oscillations, it is not necessary for antagonist enzyme E1 to be activated by its product S2. If it is enzyme E1 which is inhibited by an excess of its substrate S1, the system has a saddle point. Other conditions for stability or instability of the system have been determined. If the enzyme E1, which is not inhibited by the substrate, exhibits a slow conformational transition of the mnemonical type, this transition dramatically alters the stability behavior of the system. If the mnemonical enzyme E1 were exhibiting a positive kinetic co-operativity, decreasing the rate of the conformational transition of the mnemonical enzyme will increase the stability of the whole system and will tend to damp the oscillations in the vicinity of the steady-state. If conversely the mnemonical enzyme E1 were exhibiting a negative kinetic co-operativity, decreasing the rate of the enzyme conformational transition will decrease the stability of the system and will tend to create or amplify oscillations of the system taken as a whole. If these results may be extended to more complex metabolic cycles, involving more than two enzymes, it may be tentatively considered that positive co-operativity associated with slow transition has emerged in the course of evolution in order to limit temporal instabilities of metabolic cycles. Alternatively one may speculate that the “biological function” of negative co-operativity is to create or amplify these temporal instabilities. 相似文献
822.
Adrien Rousseau Alastair G. McEwen Pierre Poussin-Courmontagne Didier Rognan Yves Nominé Marie-Christine Rio Catherine Tomasetto Fabien Alpy 《PLoS biology》2013,11(12)
Tumor necrosis factor (TNF) receptor-associated factor 4 (TRAF4) is frequently overexpressed in carcinomas, suggesting a specific role in cancer. Although TRAF4 protein is predominantly found at tight junctions (TJs) in normal mammary epithelial cells (MECs), it accumulates in the cytoplasm of malignant MECs. How TRAF4 is recruited and functions at TJs is unclear. Here we show that TRAF4 possesses a novel phosphoinositide (PIP)-binding domain crucial for its recruitment to TJs. Of interest, this property is shared by the other members of the TRAF protein family. Indeed, the TRAF domain of all TRAF proteins (TRAF1 to TRAF6) is a bona fide PIP-binding domain. Molecular and structural analyses revealed that the TRAF domain of TRAF4 exists as a trimer that binds up to three lipids using basic residues exposed at its surface. Cellular studies indicated that TRAF4 acts as a negative regulator of TJ and increases cell migration. These functions are dependent from its ability to interact with PIPs. Our results suggest that TRAF4 overexpression might contribute to breast cancer progression by destabilizing TJs and favoring cell migration. 相似文献
823.
824.
Philippe Camus Naïma Abbadi Marie-Christine Perrier Michèle Chéry Simone Gilgenkrantz 《Human genetics》1996,97(2):247-250
Rett syndrome (RS) is a neurologic disorder with an exclusive incidence in females. A nonrandom X-inactivation could provide insight into the understanding of this disease. We performed molecular analysis based on the differential methylation of the active and inactive X with probe M27ß, taking into account the parental origin of the two Xs, in 30 control girls, 8 sisters, and 30 RS girls. In 27 control an 31 RS mothers, the inactivation status of the X transmitted to their daughters was also analyzed. The results showed a significantly increased frequency of partial paternal X inactivation (> 65%) in lymphocytes from 16/30 RS compared with 4/30 controls (P = 0.001). These results do not support the hypothesis of a monogenic X-linked mutation but should be taken into account when researching the etiology of this desease. 相似文献