Abstract：
:The p53 tumor suppressor protein is a key regulator of cellular functions including responses to numerous stress signals, and triggers apoptosis in many cell types, including neurons. The major mechanisms known to regulate p53 stabilization and activation include phosphorylation and ubiquitin ligase-mediated proteasomal degradation. Cyclin-dependent kinase 5 (Cdk5), a proline-directed serine/threonine kinase, is most active in the central nervous system and plays a variety of roles in neuronal degeneration. Here, we demonstrate for the first time that Cdk5 interacts with p53 and increases its stability through posttranslational regulation, leading to accumulation of p53, particularly in the nucleus. We show that Cdk5 phosphorylates p53 on Ser15, Ser33 and Ser46 in vitro, and that increased Cdk5 activity in the nucleus mediates these phosphorylation events in response to genotoxic and oxidative stresses. Cdk5 mediates disruption of the interaction between p53 and Hdm2 (also known as Mdm2), and prevents Hdm2-induced p53 ubiquitylation and downregulation. Cdk5 additionally enhances phosphorylation-dependent binding of the p300 coactivator, inducing acetylation of p53. Cdk5-stabilized p53 protein is transcriptionally active, resulting in the induction of pro-apoptotic genes and subsequent mitochondria-mediated apoptosis in response to genotoxic or oxidative stress. Collectively, these novel findings help define the mechanisms underlying neuronal apoptosis occurring as a result of Cdk5-mediated p53 stabilization and transcriptional activation.
journal_name
J Cell Scijournal_title
Journal of cell scienceauthors
Lee JH,Kim HS,Lee SJ,Kim KTdoi
10.1242/jcs.03468subject
Has Abstractpub_date
2007-07-01 00:00:00pages
2259-71issue
Pt 13eissn
0021-9533issn
1477-9137pii
120/13/2259journal_volume
120pub_type
杂志文章abstract：:Cells synthesize ceramides in the endoplasmic reticulum (ER) as precursors for sphingolipids to form an impermeable plasma membrane. As ceramides are engaged in apoptotic pathways, cells would need to monitor their levels closely to avoid killing themselves during sphingolipid biosynthesis. How this is accomplished re...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.138933
更新日期：2014-01-15 00:00:00
abstract：:Mitogen-activated protein kinases (MAPKs) are conserved regulators of proliferation, differentiation and adaptation in eukaryotic cells. Their activity often involves changes in their subcellular localization, indicating an important role for these spatio-temporal dynamics in signal transmission. A striking model illu...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.213462
更新日期：2018-05-04 00:00:00
abstract：:The mucolipin (TRPML) subfamily of transient receptor potential (TRP) cation channels consists of three members that play various roles in the regulation of membrane and protein sorting along endo-lysosomal pathways. Loss-of-function mutations in TRPML1 cause the neurodegenerative lysosomal storage disorder, mucolipid...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.067330
更新日期：2010-09-15 00:00:00
abstract：:Lysosomal cysteine proteases from mammalian cells and plants are regulated by endogenous tight-binding inhibitors from the cystatin superfamily. The presence of cystatin-like inhibitors in lower eukaryotes such as protozoan parasites has not yet been demonstrated, although these cells express large quantities of cyste...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：2001-11-01 00:00:00
abstract：:In a wild population of the American newt Notophthalmus viridescens 15 females out of a total of 94 were found to be heterozygous for a paracentric inversion which includes almost the whole of the longer arm of the smallest chromosome (XI). The inversion was recognized in preparations of lampbrush chromosomes because ...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1977-04-01 00:00:00
abstract：:A tissue culture system for epithelial cells derived from male human foetal genital ducts has been established. The cells show morphological and biochemical characteristics of ductal epithelial cells, and can be passaged and maintained in culture for considerable periods of time. These cells will provide a suitable sy...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1989-04-01 00:00:00
abstract：:Distribution of mitochondria as well as other intracellular organelles in mammalian cells is regulated by interphase microtubules. Here, we demonstrate a role of microtubules in the mitochondrial biogenesis using various microtubule-active drugs and human osteosarcoma cell line 143B cells and rat liver-derived RL-34 c...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：2001-01-01 00:00:00
abstract：:Vertebrate nuclear lamins form a multigene family with developmentally controlled expression. In contrast, invertebrates have long been thought to contain only a single lamin, which in Drosophila is the well-characterized lamin Dm0. Recently, however, a Drosophila cDNA clone (pG-IF) has been identified that codes for ...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1995-10-01 00:00:00
abstract：:Ryanodine receptor subtype 1 (RyR1) has been primarily characterized in skeletal muscle but several studies have revealed its expression in smooth muscle. Here, we used Ryr1-null mice to investigate the role of this isoform in Ca(2+) signaling in urinary bladder smooth muscle. We show that RyR1 is required for depolar...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.009415
更新日期：2007-11-01 00:00:00
abstract：:The events responsible for repair of DNA interstrand cross-links in mammalian cells, the proteins involved and their interactions with each other are poorly understood. The present study demonstrates that the structural protein nonerythroid alpha spectrin (alphaSpIISigma*), present in normal human cell nuclei, plays a...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.00294
更新日期：2003-03-01 00:00:00
abstract：:The mitotic spindle has long been recognized to play an essential role in determining the position of the cleavage furrow during cell division, however little is known about the mechanisms involved in this process. One attractive hypothesis is that signals from the spindle may function to induce reorganization of cort...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1996-08-01 00:00:00
abstract：:The iron-storage protein ferritin was found to be associated with highly purified coated vesicles (CV) from chicken liver. Chicken liver ferritin was morphologically similar to ferritin from horse spleen and could be isolated using a specific anti-ferritin monoclonal antibody. This antibody recognized a 240 X 10(3) Mr...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1989-02-01 00:00:00
abstract：:Development of the nematocyst-taeniocyst complex in the four-zooid stage of a dinoflagellate, Polykrikos kofoidi, was studied by electron microscopy. We observed the following stages: formation of large spherical bodies in islets of cytoplasm containing extensive rough endoplasmic reticulum and Golgi complexes; differ...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1983-09-01 00:00:00
abstract：:The full-length primary structure and expression profile of a novel unconventional myosin heavy chain, human myosin-IXb, is described. The primary structure of this myosin predicts a 229 kDa protein that together with its recently described rat homolog, myr 5, is the ninth class of myosins to be identified. In compari...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1996-03-01 00:00:00
abstract：:Axenically grown cells of D. discoideum Ax-2 harvested in the log phase of growth, cohere rapidly when shaken in phosphate buffer. After 3.5 days in the stationary phase of growth, cells become completely non-cohesive. Although they do not stick to each other, stationary phase cells do stick to both log phase cells an...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1979-06-01 00:00:00
abstract：:Identification of the cell surface glycoproteins is an essential requirement for elucidating the mechanisms that mediate intercellular adhesion and cell migration in gastrulating amphibian embryos. In our experiments the glycoproteins present at the surface of isolated cells at blastula and gastrula stages were labell...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1986-06-01 00:00:00
abstract：:The E-cadherin-catenin complex regulates Ca(2+)-dependent cell-cell adhesion and is localized to the basolateral membrane of polarized epithelial cells. Uncoupling beta-catenin from E-cadherin by deletion or substitution mutations causes accumulation of these proteins in intracellular compartments, including the trans...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.03489
更新日期：2007-12-15 00:00:00
abstract：:Xenopus egg extracts, which support nuclear assembly and DNA replication, were functionally depleted of lamin LIII by inoculating them with monoclonal anti-lamin antibodies. Phase-contrast microscopy and electron-microscopy studies indicated that lamin-depleted extracts supported efficient chromatin decondensation, an...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1991-03-01 00:00:00
abstract：:Planar cell polarity (PCP) has been demonstrated in the epithelium of organisms from flies to humans. Recent research has revealed that the planar organization of cells requires a conserved set of genes, known as the PCP genes. Tbe PCP proteins Frizzled (Fz) and Dishevelled (Dsh) function as key players in PCP signall...
journal_title：Journal of cell science
pub_type： 杂志文章,评审
doi：10.1242/jcs.00973
更新日期：2004-02-01 00:00:00
abstract：:The tachyzoite stage of the protozoan parasite Toxoplasma gondii has two populations of microtubules: spindle microtubules and subpellicular microtubules. To determine how these two microtubule populations are regulated, we investigated microtubule behavior during the cell cycle following treatment with microtubule-di...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：2002-03-01 00:00:00
abstract：:Nearly all intermediate filament (IF) proteins share two sequence motifs located at the N- and the C-terminal ends of their helical rod domain ('coil 1a' and 'coil 2b', respectively). To examine the structural role of the coil 2b motif, we have performed in vitro assembly studies and in vivo microinjection experiments...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1992-05-01 00:00:00
abstract：:Host/symbiont specificity has been investigated in non-symbiotic and aposymbiotic brown and green hydra infected with various free-living and symbiotic species and strains of Chlorella and Chlorococcum. Morphology and ultrastructure of the symbioses obtained have been compared. Aposymbiotic Swiss Hydra viridis and Jap...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1986-12-01 00:00:00
abstract：:Niemann-Pick disease type C (NPC) is an inherited lipid storage disorder caused by mutations in NPC1 or NPC2. NPC1 is a polytopic glycoprotein that contains a sterol-sensing domain, whereas NPC2 is a soluble protein that contains an MD-2-like lipid-recognition domain. In the current study, we addressed the hypothesis ...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.02993
更新日期：2006-07-01 00:00:00
abstract：:5'AMP nucleotidase activity was localized by electron microscopy in Dictyostelium discoideum during cell differentiation. In addition, the activity was assayed by micro enzymic methods in sections dissected from specific cellular regions of lyophilized individuals. The results of the 2 procedures were in agreement, de...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1980-10-01 00:00:00
abstract：:Neurite outgrowth is known as a slow (days) process occurring in nerve cells and neurons during neurotrophin treatment and upon transfer to culture, respectively. Using Y27632, a drug that induces activation of Rac1, a downstream step of the neurotrophin signaling cascade, we have identified a new form of outgrowth, w...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.059634
更新日期：2010-01-15 00:00:00
abstract：:Rubella virus (RV) envelope glycoproteins E1 and E2 are targeted to the Golgi as heterodimers. While E2 contains a transmembrane Golgi retention signal, E1 is arrested in a pre-Golgi compartment in the absence of E2, and appears to require heterodimerization in order to reach the Golgi. Various forms of E1 with deleti...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1996-06-01 00:00:00
abstract：:The structure of the nuclear pore complex (NPC) has been previously studied by many different electron microscopic techniques. Recently, scanning electron microscopes have been developed that can visualise biologically relevant structural detail at the same level of resolution as transmission electron microscopes and ...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1993-09-01 00:00:00
abstract：:S100 proteins have attracted great interest in recent years because of their cell- and tissue-specific expression and association with various human pathologies. Most S100 proteins are small acidic proteins with calcium-binding domains - the EF hands. It is thought that this group of proteins carry out their cellular ...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：2002-08-01 00:00:00
abstract：:Although the long-term effects of all-trans retinoic acid (RA) on neuronal growth and differentiation have been intensively studied, nothing is known about its effect on synaptic transmission. Here we show that RA rapidly and specifically enhances the spontaneous acetylcholine release at developing neuromuscular synap...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.01153
更新日期：2004-06-15 00:00:00
abstract：:Disruption of the sarcoglycan complex leads to muscle membrane instability and muscular dystrophy in humans and mice. Through the dystrophin glycoprotein complex, sarcoglycan participates in connecting the internal cytoskeleton to the membrane and the extracellular matrix. Integrin alpha7beta1 is also a transmembrane ...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.01234
更新日期：2004-08-01 00:00:00
