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Functional Inactivation (functional + inactivation)

Distribution by Scientific Domains

Life Sciences	60%
Medical Sciences	40%

Selected Abstracts

The auxin-binding protein 1 is essential for the control of cell cycle

THE PLANT JOURNAL, Issue 2 2007
Karine M. David
Summary The phytohormone auxin has been known for >50 years to be required for entry into the cell cycle. Despite the critical effects exerted by auxin on the control of cell division, the molecular mechanism by which auxin controls this pathway is poorly understood, and how auxin is perceived upstream of any change in the cell cycle is unknown. Auxin Binding Protein 1 (ABP1) is considered to be a candidate auxin receptor, triggering early modification of ion fluxes across the plasma membrane in response to auxin. ABP1 has also been proposed to mediate auxin-dependent cell expansion, and is essential for early embryonic development. We investigated whether ABP1 has a role in the cell cycle. Functional inactivation of ABP1 in the model plant cell system BY2 was achieved through cellular immunization via the conditional expression of a single-chain fragment variable (scFv). This scFv was derived from a well characterized anti-ABP1 monoclonal antibody previously shown to block the activity of the protein. We demonstrate that functional inactivation of ABP1 results in cell-cycle arrest, and provide evidence that ABP1 plays a critical role in regulation of the cell cycle by acting at both the G1/S and G2/M checkpoints. We conclude that ABP1 is essential for the auxin control of cell division and is likely to constitute the first step of the auxin-signalling pathway mediating auxin effects on the cell cycle. [source]

The correlation between cerebral glucose metabolism and benzodiazepine receptor density in the acute vegetative state

EUROPEAN JOURNAL OF NEUROLOGY, Issue 6 2002
J. Rudolf
This paper compares the results of parallel positron emission tomography (PET) studies of regional cerebral glucose metabolism with the radiotracer 18F-fluorodeoxyglucose (FDG) and benzodiazepine receptor (BZR) density by PET using the BZR ligand 11C-flumazenil (FMZ), a tracer of neuronal integrity, in nine patients with acute vegetative state (AVS, duration <1 month). Overall glucose utilization was significantly reduced in AVS in comparison with age-matched controls (global metabolic rate for glucose 26 ,mol/100 g/min in AVS vs. 31 ,mol/100 g/min in controls). FMZ-PET demonstrated a considerable reduction of BZR binding sites in all cortical regions that grossly corresponded to the extent of reduction of cerebral glucose metabolism assessed with FDG-PET, whilst the cerebellum was spared from neuronal loss. In controls, cortical relative flumazenil binding was not lower than five times the average white matter activity, whilst in AVS, nearly all values were below this threshold. There was no relevant overlap of the data of relative flumazenil binding between both groups. The comparison of FDG- and FMZ-PET findings in AVS demonstrates that alterations of cerebral glucose consumption do not represent mere functional inactivation, but irreversible structural brain damage. [source]

PD-1 signalling in CD4+ T cells restrains their clonal expansion to an immunogenic stimulus, but is not critically required for peptide-induced tolerance

IMMUNOLOGY, Issue 1 2010
Joanne E. Konkel
Summary The ultimate outcome of T-cell recognition of peptide,major histocompatibility complex (MHC) complexes is determined by the molecular context in which antigen presentation is provided. The paradigm is that, after exposure to peptides presented by steady-state dendritic cells (DCs), inhibitory signals dominate, leading to the deletion and/or functional inactivation of antigen-reactive T cells. This has been utilized in a variety of models providing peptide antigen in soluble form in the absence of adjuvant. A co-inhibitory molecule of considerable current interest is PD-1. Here we show that there is the opportunity for the PD-1/PD-L1 interaction to function in inhibiting the T-cell response during tolerance induction. Using traceable CD4+ T-cell receptor (TCR) transgenic cells, together with a blocking antibody to disrupt PD-1 signalling, we explored the roles of PD-1 in the induction of tolerance versus a productive immune response. Intact PD-1 signalling played a role in limiting the extent of CD4+ T-cell accumulation in response to an immunogenic stimulus. However, PD-1 signalling was not required for either the induction, or the maintenance, of peptide-induced tolerance; a conclusion underlined by successful tolerance induction in TCR transgenic cells genetically deficient for PD-1. These observations contrast with the reported requirement for PD-1 signals in CD8+ T-cell tolerance. [source]

Resistance to UV-induced apoptosis in human keratinocytes during accelerated senescence is associated with functional inactivation of p53

JOURNAL OF CELLULAR PHYSIOLOGY, Issue 1 2004
V. Chaturvedi
Compared to proliferating keratinocytes (KCs), growth-arrested KCs are relatively resistant to UV-light induced apoptosis. When KCs undergo confluency, or following exposure to anti-proliferative agents such as IFN-, plus a phorbol ester,12- O -tetradecanoylyphorbol-13-acetate (TPA), they convert from a proliferative to a nonproliferative state resembling senescence. Since p53 regulates UV-induced apoptosis of KCs, this report further characterizes p53 half-life, post-translational modifications, and transcriptional activity using cultured human KCs and living epidermal equivalents. The half-life of p53 in KCs was longer than fibroblasts (greater than approximately 3 h vs. 30 min). Exposure of proliferating KCs to UV-light induces post-translational modifications of p53 including acetylation of lysine-382 residues. By contrast, KCs undergoing irreversible growth arrest following confluency, or exposure to IFN-, plus TPA, were resistant to UV-induced apoptosis, and failed to undergo the acetylation modification of p53. Exposure of KCs to IFN-, plus TPA reduced total cellular p53 levels and reduced the transcriptional activity of p53. Addition of Trichostatin A (TSA), an inhibitor of de-acetylation, increased acetylation of lysine-382 in confluent KCs, thereby enhancing susceptibility of confluent cultures to UV-induced apoptosis. Pre-treatment of epidermal equivalents with IFN-, plus TPA also blocked UV-light induced increase in p53 levels, and reduced apoptosis. In conclusion, these studies demonstrate that growth arrested KCs may resist UV-light induced apoptosis by inactivating the pro-apoptotic function of p53. J. Cell. Physiol. 198: 100,109, 2004. © 2003 Wiley-Liss, Inc. [source]