Search results for "Biological Phenomena"

Amyloid Beta-Mediated Changes in Synaptic Function and Spine Number of Neocortical Neurons Depend on NMDA Receptors

2021

Onset and progression of Alzheimer’s disease (AD) pathophysiology differs between brain regions. The neocortex, for example, is a brain region that is affected very early during AD. NMDA receptors (NMDARs) are involved in mediating amyloid beta (Aβ) toxicity. NMDAR expression, on the other hand, can be affected by Aβ. We tested whether the high vulnerability of neocortical neurons for Aβ-toxicity may result from specific NMDAR expression profiles or from a particular regulation of NMDAR expression by Aβ. Electrophysiological analyses suggested that pyramidal cells of 6-months-old wildtype mice express mostly GluN1/GluN2A NMDARs. While synaptic NMDAR-mediated currents are unaltered in 5xFAD …

2013

MicroRNAs of the miR-302 cluster are involved in early embryonic development and somatic cell reprogramming. Expression of the miR-302 gene is regulated by the binding of the pluripotency factors Oct4, Sox2 and Nanog to the miR-302 promoter. The specific expression pattern of the miR-302 gene suggested that additional transcription factors might be involved in its regulation. Here, we show that the miR-302 promoter is a direct target of the Wnt/β-catenin signaling pathway. We found that the miR-302 promoter contains three different functional Tcf/Lef binding sites. Two of the three sites were located within the cluster of Oct4/Sox2/Nanog binding sites and were essential for Wnt/β-catenin-me…

RNAi mediated acute depletion of Retinoblastoma protein (pRb) promotes aneuploidy in human primary cells via micronuclei formation

2009

BACKGROUND: Changes in chromosome number or structure as well as supernumerary centrosomes and multipolar mitoses are commonly observed in human tumors. Thus, centrosome amplification and mitotic checkpoint dysfunctions are believed possible causes of chromosomal instability. The Retinoblastoma tumor suppressor (RB) participates in the regulation of synchrony between DNA synthesis and centrosome duplication and it is involved in transcription regulation of some mitotic genes. Primary human fibroblasts were transfected transiently with short interfering RNA (siRNA) specific for human pRb to investigate the effects of pRb acute loss on chromosomal stability. RESULTS: Acutely pRb-depleted fibr…

Molecular evolution of the metazoan protein kinase C multigene family

1996

Protein kinases C (PKCs) comprise closely related Ser/Thr kinases, ubiquitously present in animal tissues ; they respond to second messengers, e.g., Ca2+ and/or diacylglycerol, to express their activities. Two PKCs have been sequenced from Geodia cydonium, a member of the lowest multicellular animals, the sponges (Porifera). One sponge G. cydonium PKC, GCPKC1, belongs to the ''novel'' (Ca2+-independent) PKC (nPKC) subfamily while the second one, GCPKC2, has the hall-marks of the ''conventional'' (Ca2+-dependent) PKC (cPKC) subfamily. The alignment of the Ser/Thr catalytic kinase domains, of the predicted aa sequences for these cDNAs with respective segments from previously reported sequence…

The Mitochondrial Targeting Chaperone 14-3-3ε Regulates a RIG-I Translocon that Mediates Membrane Association and Innate Antiviral Immunity

2012

SummaryRIG-I is a cytosolic pathogen recognition receptor that initiates immune responses against RNA viruses. Upon viral RNA recognition, antiviral signaling requires RIG-I redistribution from the cytosol to membranes where it binds the adaptor protein, MAVS. Here we identify the mitochondrial targeting chaperone protein, 14-3-3ε, as a RIG-I-binding partner and essential component of a translocation complex or “translocon” containing RIG-I, 14-3-3ε, and the TRIM25 ubiquitin ligase. The RIG-I translocon directs RIG-I redistribution from the cytosol to membranes where it mediates MAVS-dependent innate immune signaling during acute RNA virus infection. 14-3-3ε is essential for the stable inte…

A central nervous system-focused treatment approach for people with frozen shoulder: protocol for a randomized clinical trial

2019

Background: Frozen shoulder (FS) is a musculoskeletal condition of poorly understood etiology that results in shoulder pain and large mobility deficits. Despite some physical therapy interventions, such as joint mobilization and exercise, having shown therapeutic benefit, a definitive treatment does not currently exist. The aim of this study will be to compare the effectiveness of a central nervous system (CNS)-directed treatment program versus a standard medical and physical therapy care program on outcomes in participants with FS. Methods/design: The study is a two-group, randomized clinical trial with blinding of participants and assessors. Participants will be recruited via referrals fr…

Cellular Inhibitor of Apoptosis Protein-1 (cIAP1) Can Regulate E2F1 Transcription Factor-mediated Control of Cyclin Transcription

2011

International audience; The inhibitor of apoptosis protein cIAP1 (cellular inhibitor of apoptosis protein-1) is a potent regulator of the tumor necrosis factor (TNF) receptor family and NF-B signaling pathways in the cytoplasm. However, in some primary cells and tumor cell lines, cIAP1 is expressed in the nucleus, and its nuclear function remains poorly understood. Here, we show that the N-terminal part of cIAP1 directly interacts with the DNA binding domain of the E2F1 transcription factor. cIAP1 dramatically increases the transcriptional activity of E2F1 on synthetic and CCNE promoters. This function is not conserved for cIAP2 and XIAP, which are cytoplasmic proteins. Chromatin immunoprec…

Melatonin induces transcriptional regulation of Bim by FoxO3a in HepG2 cells

2012

Background: Melatonin induces apoptosis in many different cancer cell lines, including hepatocellular carcinoma cells. However, the responsible pathways have not been clearly elucidated. A member of the forkhead transcription factors' family, FoxO3a, has been implicated in the expression of the proapoptotic protein Bim (a Bcl-2-interacting mediator of cell death). In this study, we used human HepG2 liver cancer cells as an in vitro model to investigate whether melatonin treatment induces Bim through regulation by the transcription factor FoxO3a. Methods: Cytotoxicity of melatonin was compared in HepG2 hepatoblastoma cells and primary human hepatocytes. Proapoptotic Bim expression was analys…

Direct Activation of Bax by p53 Mediates Mitochondrial Membrane Permeabilization and Apoptosis

2004

The tumor suppressor p53 exerts its anti-neoplastic activity primarily through the induction of apoptosis. We found that cytosolic localization of endogenous wild-type or trans-activation–deficient p53 was necessary and sufficient for apoptosis. p53 directly activated the proapoptotic Bcl-2protein Bax in the absence of other proteins to permeabilize mitochondria and engage the apoptotic program. p53 also released both proapoptotic multidomain proteins and BH3-only proteins [Proapoptotic Bcl-2family proteins that share only the third Bcl-2homology domain (BH3)] that were sequestered by Bcl-xL. The transcription-independent activation of Bax by p53 occurred with similar kinetics and concentra…

IAP proteins as targets for drug development in oncology

2013

Laurence Dubrez,1,2 Jean Berthelet,1,2 Valérie Glorian,1,21Institut National de la Santé et de la Recherche Médicale (Inserm), Dijon, France; 2Université de Bourgogne, Dijon, FranceAbstract: The inhibitors of apoptosis (IAPs) constitute a family of proteins involved in the regulation of various cellular processes, including cell death, immune and inflammatory responses, cell proliferation, cell differentiation, and cell motility. There is accumulating evidence supporting IAP-targeting in tumors: IAPs regulate various cellular processes that contribute to tumor development, such as cell death, cell proliferation, and cell migration; their expressio…