Abstract：
:Pharmacological inhibitors of JNK (SP600125) and p38 (PD169316) sensitize tumor cells to Fas-mediated apoptosis. PD169316 is less potent than SP600125 and diminishes its effect when present together. Because the p38 isoforms that promote (p38alpha) or inhibit (p38beta) apoptosis are both suppressed by PD169316, we investigated their regulatory involvement in Fas-signaling. We report here, that p38alpha, but not p38beta, exerts its proapoptotic effect by inhibiting the phosphorylation and presence of c-FLIPS, but not c-FLIPL, in the DISC to promote caspase-8 activation and type I signaling in Fas-activated Jurkat cells. Its effect was enhanced by enforced expression of Flag-tagged p38alpha and was attenuated by its inactive mutant (p38alpha-AGF) or by translational silencing. By contrast, type II signaling was facilitated by p38alpha-dependent mitochondrial presence of tBid and inhibition of Bcl-2 (Ser70) phosphorylation as well as by p38alpha/beta-dependent mitochondrial localization of Bax and inhibition of phosphorylation of Bad (Ser112/Ser155). Potentiation of Fas-mediated apoptosis by the inhibition of JNK1/2 correlated with the loss of Bad (Ser136) phosphorylation and was dependent on the stimulatory effect of p38alpha on DISC and the downstream effects of both p38alpha and p38beta. These data underscore the need to reassess the findings obtained with pan-p38 inhibitors and suggest that activation of p38alpha coupled with targeted inhibition of p38beta and JNK1/2 should optimally sensitize tumor cells to Fas-mediated apoptosis.
journal_name
J Cell Scijournal_title
Journal of cell scienceauthors
Tourian L Jr,Zhao H,Srikant CBdoi
10.1242/jcs.01573keywords:
subject
Has Abstractpub_date
2004-12-15 00:00:00pages
6459-71issue
Pt 26eissn
0021-9533issn
1477-9137pii
jcs.01573journal_volume
117pub_type
杂志文章abstract：:The large GTPase dynamin is a mechanoenzyme that participates in the scission of nascent vesicles from the plasma membrane. Recently, dynamin has been demonstrated to associate with the Golgi apparatus in mammalian cells by morphological and biochemical methods. Additional studies using a well characterized, cell-free...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：2000-06-01 00:00:00
abstract：:Promyelocytic leukemia nuclear bodies (PML-NBs) are mobile subnuclear organelles formed by PML and Sp100 protein. They have been reported to have a role in transcription, DNA replication and repair, telomere lengthening, cell cycle control and tumor suppression. We have conducted high-resolution 4Pi fluorescence laser...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.053496
更新日期：2010-02-01 00:00:00
abstract：:TRF1 is a key component of the telomere-capping complex and binds double-strand telomeric DNA as homodimers. So far, it is not clear whether TRF1 dimerization coincides with its telomere binding or is actively controlled before it binds the telomere, and in the latter case, how this event might affect its telomere ass...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.089672
更新日期：2011-11-01 00:00:00
abstract：:Alix is a cytosolic protein in mammalian cells that was originally identified on the basis of its association with pro-apoptotic signaling. More recent evidence has established that Alix has a hand in regulating other cellular mechanisms, including endocytic membrane trafficking and cell adhesion. Although Alix appear...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.03072
更新日期：2006-08-01 00:00:00
abstract：:Sustained neurotransmission requires the tight coupling of synaptic vesicle (SV) exocytosis and endocytosis. The mechanisms underlying this coupling are poorly understood. We tested the hypothesis that a cGMP-dependent protein kinase (PKG), encoded by the foraging (for) gene in Drosophila melanogaster, is critical for...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.227165
更新日期：2019-04-05 00:00:00
abstract：:Yeast Reb1 and its mammalian ortholog TTF1 are conserved Myb-type DNA-binding proteins that bind to specific sites near the 3'-end of rRNA genes (rDNA). Here, they participate in the termination of transcription driven by RNA polymerase I and block DNA replication forks approaching in the opposite direction. We found ...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.070987
更新日期：2011-01-01 00:00:00
abstract：:The water pipes of elongating plant organs are the result of programmed cell death and are formed by the walls of dead and empty protoxylem elements. These protoxylem elements are passively elongated many times by the surrounding tissue before they are replaced and collapse. Well-known adaptations for this unique task...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.00966
更新日期：2004-03-01 00:00:00
abstract：:The coordinated cellular responses to physiological stress are known to be effected in part by the activation of heat-shock factor 1, a transcriptional activator protein capable of binding to, and inducing transcription from genes containing heat shock elements. Other stress responsive signal transduction pathways als...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1996-05-01 00:00:00
abstract：:This study uses electron tomography linked to a variety of other EM methods to provide an integrated view of the flagellar pocket and basal body area of the African trypanosome procyclic trypomastigote. We reveal the pocket as an asymmetric membranous 'balloon' with two boundary structures. One of these - the collar -...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.045740
更新日期：2009-04-15 00:00:00
abstract：:In trypanosomes, the flagellum is rooted in the flagellar pocket, a surface micro-domain that is the sole site for endocytosis and exocytosis. By analysis of anterograde or retrograde intraflagellar transport in IFT88RNAi or IFT140RNAi mutant cells, we show that elongation of the new flagellum is not required for flag...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.035626
更新日期：2008-11-15 00:00:00
abstract：:Microtubules stimulate contractile-ring formation in the equatorial cortex and simultaneously suppress contractility in the polar cortex; how they accomplish these differing activities is incompletely understood. We measured the behavior of GFP-actin in mammalian cells treated with nocodazole under conditions that eit...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.027052
更新日期：2008-07-15 00:00:00
abstract：:We investigated mechanisms of the p73alpha-mediated repression of the platelet-derived growth factor beta-receptor (PDGFRB) promoter caused by its interaction with NF-Y. Treatment of cells with the histone deacetylase (HDAC) inhibitor, Trichostatin A, increases PDGFRB promoter activity through the CCAAT motif and coun...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.01384
更新日期：2004-10-15 00:00:00
abstract：:Purified nuclei retaining a high degree of ultrastructural integrity were isolated by conventional centrifugation techniques. The cytoplasmic surface of these nuclei was iodinated using lactoperoxidase immobilized onto giant Sepharose beads; thus the outer nuclear membrane and the cytoplasmic surface of nuclear pore c...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1980-06-01 00:00:00
abstract：:Basonuclin is a zinc finger protein mainly expressed in keratinocytes of the basal layer of epidermis and the outer root sheath of hair follicles. It is also found in abundance in the germ cells of testis and ovary. In cultured keratinocytes, basonuclin is associated with chromatin in all phases of the cell cycle, inc...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1999-09-01 00:00:00
abstract：:Borrelia burgdorferi is the causative agent of Lyme disease, a multisystemic disorder affecting primarily skin, joints and nervous system. Successful internalization and intracellular processing of borreliae by immune cells like macrophages is decisive for the outcome of a respective infection. Here, we use for the fi...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.252320
更新日期：2020-12-30 00:00:00
abstract：:Abnormal cardiac valve morphogenesis is a common cause of human congenital heart disease. The molecular mechanisms regulating endocardial cell proliferation and differentiation into cardiac valves remain largely unknown, although great progress has been made on the endocardial contribution to the atrioventricular cush...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.116996
更新日期：2013-03-15 00:00:00
abstract：:It is becoming clear that mechanical stimuli are crucial factors in regulating the biology of the cell, but the short-term structural response of a cell to mechanical forces remains relatively poorly understood. We mechanically stimulated cells transiently expressing actin-EGFP with controlled forces (0-20 nN) in orde...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.088302
更新日期：2012-02-01 00:00:00
abstract：:In vitro experimental evidences suggest that the proteolytic degradation of the extracellular matrix (ECM) by activation of the urokinase-type plasminogen activator (uPA)/plasmin system may affect growth factor activity and bioavailability. However, no direct in vivo observations were available to support this hypothe...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1999-12-01 00:00:00
abstract：:The Arp2/3 complex is important for morphogenesis in various developmental systems, but specific in vivo roles for this complex in cells that move during morphogenesis are not well understood. We have examined cellular roles for Arp2/3 in the Caenorhabditis elegans embryo. In C. elegans, the first morphogenetic moveme...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.057562
更新日期：2009-11-01 00:00:00
abstract：:Semaphorin 3A (Sema3A), a secretory semaphorin, exerts various biological actions through a complex between neuropilin-1 and plexin-As (PlexAs). Sema3A induces retrograde signaling, which is involved in regulating dendritic localization of GluA2 (also known as GRIA2), an AMPA receptor subunit. Here, we investigated a ...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.184580
更新日期：2016-05-01 00:00:00
abstract：:As previously described, a cell surface-associated adhesive factor (AF) was separated from differentiated rat ascites hepatoma AH136B cells (forming cell islands in vivo) and highly purified by chromatography. AF synthesis by the cells was investigated by means of ultrastructural immunoperoxidase cytochemistry. Its sy...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1984-10-01 00:00:00
abstract：:The transmembrane inner nuclear membrane (INM) protein Samp1 is required for anchoring centrosomes near the nuclei. Using high-resolution fluorescence microscopy we show that Samp1 is distributed in a distinct and characteristic pattern in the nuclear envelope (NE), where it partially colocalizes with the LINC complex...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.078923
更新日期：2011-06-15 00:00:00
abstract：:Expression of a dominant negative fragment of the spectrin family member Syne-1 causes an accumulation of binucleate cells, suggesting a role for this protein in cytokinesis. An association of this fragment with the C-terminal tail domain of the kinesin II subunit KIF3B was identified by yeast two-hybrid and co-precip...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.00892
更新日期：2004-02-01 00:00:00
abstract：:The key read-out of Wnt signalling is a change in the transcriptional profile of the cell, which is driven by β-catenin. β-catenin levels are normally kept low by a phosphorylation event that is mediated by glycogen synthase kinase 3 (GSK3, α- and β-isoforms), which targets β-catenin for ubiquitylation and proteasomal...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.091991
更新日期：2011-11-01 00:00:00
abstract：:The auto-catalytic activation of the cyclin-dependent kinase Cdc2 or MPF (M-phase promoting factor) is an irreversible process responsible for the entry into M phase. In Xenopus oocyte, a positive feed-back loop between Cdc2 kinase and its activating phosphatase Cdc25 allows the abrupt activation of MPF and the entry ...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1999-11-01 00:00:00
abstract：:Megalin is a receptor expressed by embryonic epithelia that mediates endocytosis of numerous ligands, including sonic hedgehog (Shh) and retinol, the precursor to retinoic acid (RA). The importance of Shh and RA signaling in neurodevelopment, combined with the fact that megalin-deficient mice show profound neurodevelo...
journal_title：Journal of cell science
pub_type： 杂志文章,评审
doi：10.1242/jcs.00313
更新日期：2003-03-15 00:00:00
abstract：:In culture, cell confluence generates signals that commit actively growing keratinocytes to exit the cell cycle and differentiate to form a stratified epithelium. Using a comparative proteomic approach, we studied this 'confluence switch' and identified a new pathway triggered by cell confluence that regulates basemen...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.096289
更新日期：2012-09-15 00:00:00
abstract：:It remains unclear how GPI-anchored proteins (GPIAPs), which lack cytoplasmic domains, transduce signals triggered by specific ligation. Such signal transduction has been speculated to require the ligated GPIAP to associate with membrane-spanning proteins that communicate with obligate cytoplasmic proteins. Transient ...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.049346
更新日期：2009-11-01 00:00:00
abstract：:The Arabidopsis AINTEGUMENTA (ANT) gene, which encodes an APETALA2 (AP2)-like transcription factor, controls plant organ cell number and organ size throughout shoot development. ANT is thus a key factor in the development of plant shoots. Here, we have found that ANT plays an essential role in conferring salt toleranc...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.172072
更新日期：2015-08-01 00:00:00
abstract：:The protozoan parasite Giardia lamblia has the unusual morphology of bearing two equal-sized nuclei. This organism probably represents the earliest diverging lineage of eukaryotes, suggesting that its biological tactics may be transitional. To begin to understand the role played by the two equal-sized nuclei in this o...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1990-03-01 00:00:00
