Abstract：
:Heat shock transcription factor 1 (HSF1) regulates the expression of a wide array of genes, controls the expression of heat shock proteins (HSPs) as well as cell growth. Although acute depletion of HSF1 induces cellular senescence, the underlying mechanisms are poorly understood. Here, we report that HSF1 depletion-induced senescence (HDIS) of human diploid fibroblasts (HDFs) was independent of HSP-mediated proteostasis but dependent on activation of the p53-p21 pathway, partly because of the increased expression of dehydrogenase/reductase 2 (DHRS2), a putative MDM2 inhibitor. We observed that HDIS occurred without decreased levels of major HSPs or increased proteotoxic stress in HDFs. Additionally, VER155008, an inhibitor of HSP70 family proteins, increased proteotoxicity and suppressed cell growth but failed to induce senescence. Importantly, we found that activation of the p53-p21 pathway resulting from reduced MDM2-dependent p53 degradation was required for HDIS. Furthermore, we provide evidence that increased DHRS2 expression contributes to p53 stabilization and HDIS. Collectively, our observations uncovered a molecular pathway in which HSF1 depletion-induced DHRS2 expression leads to activation of the MDM2-p53-p21 pathway required for HDIS.
journal_name
J Cell Scijournal_title
Journal of cell scienceauthors
Oda T,Sekimoto T,Kurashima K,Fujimoto M,Nakai A,Yamashita Tdoi
10.1242/jcs.210724subject
Has Abstractpub_date
2018-05-08 00:00:00issue
9eissn
0021-9533issn
1477-9137pii
jcs.210724journal_volume
131pub_type
杂志文章abstract：:The invasiveness of cells is correlated with the presence of dynamic actin-rich membrane structures called invadopodia, which are membrane protrusions that are associated with localized polymerization of sub-membrane actin filaments. Similar to focal adhesions and podosomes, invadopodia are cell-matrix adhesion sites....
journal_title：Journal of cell science
pub_type： 杂志文章,评审
doi：10.1242/jcs.052704
更新日期：2009-09-01 00:00:00
abstract：:A high molecular weight tight junction-associated protein, ZO-1, has been demonstrated in liver (hepatocytes) and in both epithelium and endothelium. We carried out studies to examine the presence of the protein in vascular endothelial cell cultures and several other types of cultured cells, and the relationship betwe...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1990-10-01 00:00:00
abstract：:In skeletal muscle, the triad is a structure comprising a transverse (T)-tubule and sarcoplasmic reticulum (SR) cisternae. Triads constitute the basis of excitation-contraction coupling as the cradle of the Ca2+ release complex. We have shown previously that triadin, a member of this complex, has shaping properties on...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.188862
更新日期：2016-10-15 00:00:00
abstract：:Human SW-13 cells express the intermediate filament protein vimentin in a mosaic pattern (Hedberg, K. K. and Chen, L. B. (1986). Exp. Cell Res. 163, 509-517). We have isolated SW-13 clones that do (vim+) or do not (vim-) synthesize vimentin as analyzed using anti-intermediate filament immunofluorescence, electron micr...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1994-06-01 00:00:00
abstract：:Mutation of the LMNA gene, encoding nuclear lamin A and lamin C (hereafter lamin A/C), is a common cause of familial dilated cardiomyopathy (DCM). Among Finnish DCM patients, the founder mutation c.427T>C (p.S143P) is the most frequently reported genetic variant. Here, we show that p.S143P lamin A/C is more nucleoplas...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.184150
更新日期：2016-07-15 00:00:00
abstract：:Here, we identify a role for the matrilin-2 (Matn2) extracellular matrix protein in controlling the early stages of myogenic differentiation. We observed Matn2 deposition around proliferating, differentiating and fusing myoblasts in culture and during muscle regeneration in vivo. Silencing of Matn2 delayed the express...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.141556
更新日期：2014-08-01 00:00:00
abstract：:During muscle development myosin molecules form symmetrical thick filaments, which integrate with the thin filaments to produce the regular sarcomeric lattice. In Drosophila indirect flight muscles (IFMs) the details of this process can be studied using genetic approaches. The weeP26 transgenic line has a GFP-encoding...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.110361
更新日期：2013-01-01 00:00:00
abstract：:Freeze-fracture of fixed and unfixed tissue, lanthanum tracer and conventional thin-section studies have revealed 2 new types of septate junction in the class Anthozoa, phylum Coelenterata. These new junctions have the 15-18-nm intercellular spacing of all other described septate junctions and are found around the api...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1980-04-01 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
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journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1994-03-01 00:00:00
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journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.00325
更新日期：2003-03-15 00:00:00
abstract：:Compartmentalization of membrane transport and signaling processes is of pivotal importance to eukaryotic cell function. While plasma membrane compartmentalization and dynamics are well known to depend on the scaffolding function of septin GTPases, the roles of septins at intracellular membranes have remained largely ...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.225557
更新日期：2019-02-01 00:00:00
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journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.194019
更新日期：2016-10-15 00:00:00
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journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.076505
更新日期：2011-01-01 00:00:00
abstract：:Through serial thin-section analysis of rat mammary epithelial cells, the number of centrioles per cell and their intracellular location were determined. In all developmental stages (e.g. virginal, pregnant, lactation, involution), each epithelial cell contained a single centriole that was located in the apical region...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1984-12-01 00:00:00
abstract：:Diversity of cell lineages within glandular organs is generated postnatally by differentiation of committed progenitor cells. Fundamental regulatory aspects of this process are not understood. The mouse submandibular salivary gland (SSG) served as model to assess the role of epidermal growth factor (EGF) receptor sign...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1995-06-01 00:00:00
abstract：:Mitochondria play essential roles in cellular energy processes, including ATP production, control of reactive oxygen species (ROS) and apoptosis. While mitochondrial function is regulated by the dynamics of fusion and fission, mitochondrial homeostasis remains incompletely understood. Recent studies implicate dynamin-...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.204537
更新日期：2017-07-15 00:00:00
abstract：:Onconase is an RNase with a very specific property because it is selectively toxic to transformed cells. This toxin is thought to recognize cell surface receptors, and the protection conferred by metabolic poisons against Onconase toxicity indicated that this RNase relies on endocytic uptake to kill cells. Nevertheles...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.03427
更新日期：2007-04-15 00:00:00
abstract：:The essential function of the T cell receptor (TCR) is to translate the engagement of peptides on the major histocompatibility complex (pMHC) into appropriate intracellular signals through the associated cluster of differentiation 3 (CD3) complex. The spatial organization of the TCR-CD3 complex in the membrane is thou...
journal_title：Journal of cell science
pub_type： 杂志文章,评审
doi：10.1242/jcs.226423
更新日期：2019-02-11 00:00:00
abstract：:Cells govern tissue shape by exerting highly regulated forces at sites of matrix adhesion. As the major force-bearing adhesion-receptor protein, integrins have a central role in how cells sense and respond to the mechanics of their surroundings. Recent studies have shown that a key aspect of mechanotransduction is the...
journal_title：Journal of cell science
pub_type： 杂志文章,评审
doi：10.1242/jcs.042127
更新日期：2009-01-15 00:00:00
abstract：:We investigated the link between cell movement and plasma membrane recycling using a fast-acting, temperature-sensitive mutant of the Dictyostelium SecA exocytic protein. Strikingly, most mutant cells become almost paralysed within minutes at the restrictive temperature. However, they can still sense cyclic-AMP (cAMP)...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.072876
更新日期：2010-10-01 00:00:00
abstract：:Current methodologies for targeting the mitochondrial genome for research and/or therapy development in mitochondrial diseases are restricted by practical limitations and technical inflexibility. A molecular toolbox for CRISPR-mediated mitochondrial genome editing is desirable, as this could enable targeting of mtDNA ...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.248468
更新日期：2020-09-16 00:00:00
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journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1976-11-01 00:00:00
abstract：:8-Hydroxyquinoline (HQ) chelates Mg2+ and Mn2+ and, secondarily, affects the activities of DNA and RNA polymerases. The in vivo effect of HQ has been estimated in Allium cepa L. meristems growing under new growth kinetics in the presence of this agent. HQ (at both 5 X 10(-5) M and 10(-4) M) depressed incorporation of ...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1986-02-01 00:00:00
abstract：:Heat-shock for 2 hours at 42 degrees C, or the administration for 3 hours of 100 or 150 microM cadmium chloride, inhibited the subsequent proliferation activity, induced the expression of functional differentiation markers, and caused an increase in the amount of the stress-responsive HSP70 protein in U-937 human prom...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1997-01-01 00:00:00
abstract：:The adaptive immune response depends on the interaction of T cells and antigen-presenting cells at the immune synapse. Formation of the immune synapse and the subsequent T-cell activation are highly dependent on the actin cytoskeleton. In this work, we describe that T cells express drebrin, a neuronal actin-binding pr...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.064238
更新日期：2010-04-01 00:00:00
abstract：:Increased deposition of collagen in extracellular matrix (ECM) leads to increased tissue stiffness and occurs in breast tumors. When present, this increases tumor invasion and metastasis. Precisely how this deposition is regulated and maintained in tumors is unclear. Much has been learnt about mechanical signal transd...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.180539
更新日期：2016-05-15 00:00:00
abstract：:Cytostellin, a approximately 240 kDa phosphoprotein found in all cells examined from human to yeast, is predominantly intranuclear in interphase mammalian cells and undergoes continuous redistribution during the cell cycle. Here, mammalian cytostellin is shown to localize to intranuclear regions enriched with multiple...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1994-03-01 00:00:00
abstract：:Errors in mitotic chromosome segregation can lead to DNA damage and aneuploidy, both hallmarks of cancer. To achieve synchronous error-free segregation, mitotic chromosomes must align at the metaphase plate with stable amphitelic attachments to microtubules emanating from opposing spindle poles. The astrin-kinastrin (...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.251025
更新日期：2021-01-08 00:00:00
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journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1986-08-01 00:00:00
