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At least 703 records · Page 39Linked to original sources
PubMed2001

A coordinated interplay: proteins with multiple functions in DNA replication, DNA repair, cell cycle/checkpoint control, and transcription.

In eukaryotic cells, DNA transactions such as replication, repair, and transcription require a large set of proteins. In all of these events, complexes of more than 30 polypetides appear to function in highly organized and structurally well-defined machines. We have learned in the past few years that the three essential macromolecular events, replication, repair, and transcription, have common functional entities and are coordinated by complex regulatory mechanisms. This can be documented for replication and repair, for replication and checkpoint control, and for replication and cell cycle control, as well as for replication and transcription. In this review we cover the three different protein classes: DNA polymerases, DNA polymerase accessory proteins, and selected transcription factors. The "common enzyme-different pathway strategy" is fascinating from several points of view: first, it might guarantee that these events are coordinated; second, it can be viewed from an evolutionary angle; and third, this strategy might provide cells with backup mechanisms for essential physiological tasks.

Cell Cycle↗
PubMed2003

Dynamic interplay between O-glycosylation and O-phosphorylation of nucleocytoplasmic proteins: a new paradigm for metabolic control of signal transduction and transcription.

The glycosylation of serine and threonine residues with beta-O-linked N-acetylglucosamine (O-GlcNAc) is an abundant posttranslational modification of nuclear and cytoplasmic proteins in multicellular eukaryotes. This highly dynamic glycosylation/deglycosylation of protein is catalyzed by the nucleocytoplasmic enzymes, UDP-G1cNAc: polypeptide O-beta-N-acetylglucosaminyltransferase (OGT)/O-beta-N-acetylglucosaminidase. OGT is required for embryonic stem cell viability and mouse ontogeny, thus O-GlcNAc is essential for the life of eukaryotes. The gene encoding O-GlcNAcase maps to a locus important to late-onset Alzheimer's disease. All known O-GlcNAc-modified proteins are also phosphoproteins that form reversible multimeric protein complexes. There is both a global and often site-specific reciprocal relationship between O-GlcNAc and O-phosphate in many cellular responses to stimuli. Thus, regulation of the protein-protein interaction(s) and/or protein function by dynamic glycosylation/phosphorylation has been hypothesized. In this chapter, we will review the current status of dynamic glycosylation/phosphorylation of several important regulatory proteins including c-Myc, estrogen receptors, Sp1, endothelial nitric oxide synthase, and beta-catenin. Various aspects of subcellular localization, association with binding partners, activity, and/or turnover of these proteins appear to be regulated by dynamic glycosylation/ phosphorylation in response to cellular signals or stages.

Animals↗
PubMed2004

CRH, stress, and major depression: a psychobiological interplay.

Major depressive disorder (MDD) is a complex disease and is one of the leading causes of disability in our society. The provoking factors are multiple; acute and chronic psychological stress, severe early trauma experiences, somatic disease, and genetic factors all play a role. This review focuses on hyperdrive of corticotropin-releasing hormone (CRH) as the fundamental neurobiological correlate of MDD. CRH plays a key role in the adaptation to acute stress, but chronic CRH hyperdrive leads to a number of disadvantageous emotional and somatic effects. The evidence that the HPA axis is hyperactive in MDD, probably as a result of a primary hyperdrive of CRH, comes from multiple sources: biochemical studies, functional HPA axis tests, neuroimaging and postmortem studies, and clinical trials with HPA axis-related compounds. The liability to develop CRH hyperdrive is probably partly genetic. For a number of relevant genes, transgenic animal studies and human association studies indicate a role in HPA axis regulation and the liability to develop CRH hyperdrive. These data are reviewed. Finally, early adverse experience can produce a lasting effect on HPA axis regulation as well, probably leading to a lifelong tendency to develop chronic CRH hyperdrive in response to stress. This has been shown in a number of animal studies, and recently some data in humans with early trauma have become available as well. Taken together, these findings allow formulating an integrative hypothesis, with CRH hyperdrive at the core, bridging the old dichotomy between biology and psychology in our thinking about MDD.

Adrenocorticotropic Hormone↗
PubMed2001

Defective interplay of activators and repressors with TFIH in xeroderma pigmentosum.

Inherited mutations of the TFIIH helicase subunits xeroderma pigmentosum (XP) B or XPD yield overlapping DNA repair and transcription syndromes. The high risk of cancer in these patients is not fully explained by the repair defect. The transcription defect is subtle and has proven more difficult to evaluate. Here, XPB and XPD mutations are shown to block transcription activation by the FUSE Binding Protein (FBP), a regulator of c-myc expression, and repression by the FBP Interacting Repressor (FIR). Through TFIIH, FBP facilitates transcription until promoter escape, whereas after initiation, FIR uses TFIIH to delay promoter escape. Mutations in TFIIH that impair regulation by FBP and FIR affect proper regulation of c-myc expression and have implications in the development of malignancy.

Blotting, Western↗
PubMed1998

Interplay between CDC2 kinase and MAP kinase pathway during maturation of mammalian oocytes.

Two principal kinases, p34cdc2 kinase and MAP kinase play a pivotal role in maturation of mammalian oocytes. In the porcine and bovine oocytes both kinases are activated around the time of germinal vesicle breakdown (GVBD). Butyrolactone I (BL I), a specific inhibitor of cdk kinases, prevents effectively and reversibly resumption of meiosis in the porcine and bovine oocytes. Neither p34cdc2 kinase nor MAP kinase are activated in oocytes inhibited in the GV stage. The bovine oocytes maintained for 48 h in the medium supplemented with BL I, progress subsequently to metaphase II in 91%, their cumuli expand optimally and after in vitro fertilization they possess two pronuclei. When the cdc2 kinase is blocked in the porcine oocytes by BL I, MAP kinase, activated by okadaic acid treatment, is able to substitute cdc2 kinase and induce GVBD. The histone H1 kinase activity sharply decreases in the metaphase II oocytes treated by BL I and one or two female pronuclei are formed. These data indicate that BL I is a useful tool either for the two step in vitro culture of mammalian oocytes or for their activation in nuclear transfer experiments.

4-Butyrolactone↗
PubMed1997

The interplay of nitric oxide and peroxynitrite with signal transduction pathways: implications for disease.

Since the discovery that at least one form of endothelium derived relaxing factor is nitric oxide (NO), numerous studies have uncovered diverse roles for this free radical in a variety of physiological and pathophysiological processes. NO production, a process mediated by a family of enzymes termed NO synthases, has been detected in most cell types. Many of the effects of NO are thought to be mediated through its direct interaction with specific and defined cell signaling pathways. The nature of such interactions are highly dependent on the concentration of NO and cell type. Furthermore, specific NO derived reaction products, such as peroxynitrite, also have the potential to effect cell signal transduction events. As with NO, this can occur through diverse mechanisms and depends on concentration and cell type. It is perhaps not surprising that the reported effects of NO in different disease states are often conflicting. In this brief overview, a framework for placing these apparently disparate properties of NO will be described and will focus on the effects of NO and peroxynitrite on signaling pathways.

Animals↗
PubMed2002

Kinetics of reaction of DNA-bound Fe(III)bleomycin with ascorbate: interplay of specific and non-specific binding.

The aerobic redox reaction of Fe(III)bleomycin (Blm) and ascorbate was examined in the absence of DNA and in the presence of 7.5 and 25 calf thymus DNA base pairs per-drug molecule, in order to investigate the effect of DNA binding on the properties of FeBlm activation and DNA strand cleavage. Under these successive conditions, the rate of initial reduction of Fe(III)Blm became progressively slower and biphasic. Using 7.5 base pairs per-molecule of FeBlm, 2-3 times as much drug reacted in the faster step as with the larger DNA to drug ratio. In each case, the more rapid process was identified with the reaction of high spin Fe(III)Blm-DNA. With the smaller ratio, dioxygen consumption, formation of HO(2)-Fe(III)Blm-DNA, and production of DNA strand breaks as measured by the formation of base propenal were largely rate limited by the initial reaction of ascorbate with Fe(III)Blm-DNA. After a burst of reaction with the larger ratio of base pairs to Fe(III)Blm, a small fraction of the total Fe(III)Blm, representing high spin Fe(III)Blm, entered a steady state as HO(2)-Fe(III)Blm-DNA. Thereafter, reaction of dioxygen and base propenal formation occurred slowly with similar first-order rate kinetics. In order to explain these results, it is hypothesized that the metal domain-linker of Fe(III)Blm adopts two conformations with respect to DNA. One, at specific binding sites, is relatively unreactive with ascorbate. The other, present at non-specific sites as HPO(4)-Fe(III)Blm, is readily reactive with ascorbate to generate HO(2)-Fe(III)Blm-DNA. At the larger base pair to drug ratio, movement of Fe(III)Blm between specific and non-specific sites to generate HO(2)-Fe(III)Blm is a necessary part of the mechanism of strand scission.

Animals↗
PubMed2002

Development of posture and locomotion: an interplay of endogenously generated activities and neurotrophic actions by descending pathways.

The adult pattern of locomotion is observed at the end of the second postnatal week in the rat. The in vitro spinal cord isolated from immature rats has served as a valuable preparation to study the mechanisms underlying the development of locomotion. Although the rat is unable to walk at birth, because of an immature posture, its spinal cord networks can generate at least two kinds of motor patterns in vitro. One activity is called 'fictive locomotion' because it shares several common features with locomotion observed in vivo. This fictive locomotor pattern is rarely observed spontaneously and its release requires either pharmacological or electrical stimulation of the spinal cord. A second endogenously generated activity observed in this preparation occurs spontaneously and exhibits phase relationships between motor outputs that are quite different from the fictive locomotor pattern. Here we review some of the developmental functions this spontaneous activity may subserve. It is likely a major trigger for the maturation of lumbar networks in the fetus, at a stage when inputs from both the periphery and supraspinal structures are weak. Pathways descending from the brainstem arrive in the lumbar enlargement during the last week in utero and the first two postnatal weeks. These pathways, through the neurotransmitters they contain, especially monoamines, are essential for the expression of some neuronal properties and may regulate several ongoing developmental processes.

Afferent Pathways↗
PubMed1996

Faulty cortisol/serotonin interplay. Psychopathological and biological characterisation of a new, hypothetical depression subtype (SeCA depression)

The hypothesis is proposed of a new subtype of depression named: stressor-precipitated, cortisol-induced, serotonin-related, anxiety/aggression-driven depression (SeCA depression). Biologically, these patients are characterized by impaired 5-HT synthesis and reduced 5-HT1A receptor sensitivity. Under normal conditions these functions proceed marginally; in times of stress they easily fail, due to sustained overproduction of cortisol. Psychopathologically this depression type shows the following characteristics: anxiety and aggression, not mood lowering, heralding a depressive episode; the personality structure shows 'character neurotic' impairments and tolerance for (certain) traumatic life events is low. As specific therapeutic agents selective 5-HT1A agonists and cortisol or CRH antagonists are proposed. Prophylactically, maintenance treatment with 5-HT1A agonists seems indicated as well as psychological interventions to increase the stressor threshold.

Aggression↗
PubMed1998

The covert interplay between perception and memory: event-related potential evidence.

Neurocognitive models of visual object identification have focussed on processes at the moment of identification, when perceivers can actually name what they see. Less well known is the timecourse of processes preceding and leading to actual identification. To track neuromental processes involved in visual identification, behavioral measures and event-related potentials (ERPs) were recorded in two experiments prior to, during and after the identification of fragmented objects, half of which had been shown in their complete versions in a previous study phase. Each object was revealed in a sequence of frames wherein the object was represented by an increasingly less and less fragmented image up to the complete version. A shift in ERPs, around 300 ms and beyond, from negativity to positivity, marked the transition from non-identification to identification. However, while for new stimuli such a shift appeared abruptly from non-identification to identification, for recently-studied objects a late positive wave emerged in response to unidentified fragments at a level just prior to overt identification. Thus, ERPs reflected covert processes associated with a successful match between the current visual information and episodic recently-stored memory traces, which predicted overt identification.

Adult↗
PubMed1999

Genomic imprinting in mammals: an interplay between chromatin and DNA methylation?

Most imprinted loci have key regulatory elements that are methylated on only one of the parental chromosomes. For several of these 'differentially methylated regions', recent studies establish that the unmethylated chromosome has a specialized chromatin organization that is characterized by nuclease hypersensitivity. The novel data raise the question of whether specific proteins and associated chromatin features regulate the allele-specificity of DNA methylation at these imprinting control elements.

Alleles↗
PubMed1994

Enhancement of B cell function as antigen-presenting cell during interplay with Th cells.

We have previously reported that C57BL/6 mouse B cells present Ag to an I-Ab-restricted and OVA-specific T cell clone, 34-7F, to secrete IL-2 but not to proliferate, whereas spleen adherent cells as APC induce a proliferative response of 34-7F cells to OVA. In this T cell response, it was examined whether B cells were stimulated during presenting Ag and acquired the ability as APC to induce proliferative Ag-response of 34-7F cells. For this aim, B cells prepared from unstimulated mouse spleen cells were cultured with 34-7F cells in the presence of OVA and then compared with unstimulated B cells for APC function in the OVA-response of 34-7F cells. Unstimulated B cells proliferated when cultured for 2 days with irradiated 34-7F cells and OVA, and the proliferation was inhibited by an anti-I-Ab mAb. B cells which had been stimulated for 2 days with 34-7F cells and OVA induced an increase in phosphatidyl inositol metabolism in 34-7F cells in the presence of Ag, whereas unstimulated B cells failed to do so. The increase was dependent on the dose of OVA and on the number of the stimulated B cells. Ag presentation by the stimulated B cells (but not by unstimulated ones), also induced IL-2R expression on 34-7F cells, which resulted in IL-2-dependent proliferation. The IL-2R expression does not depend on the possible increase in IL-2 production by the T cells, inasmuch as the activated B cells induced lower expression of IL-2 mRNA or lower secretion of IL-2 by 34-7F cells than that induced by unstimulated B cells. These results suggest that B cells receive signal(s) from 34-7F cells to enhance APC function during Ag-presentation to the T cells which do not proliferate in the response to Ag on unstimulated B cells, and that the stimulated B cells induce the proliferative response of 34-7F cells to OVA.

Animals↗