Abstract:
:The senescence-associated secretory phenotype (SASP) is a major trait of senescent cells, but the molecular regulators of SASP factor secretion are poorly understood. Mass spectrometry analysis revealed that secretory carrier membrane protein 4 (SCAMP4) levels were strikingly elevated on the surface of senescent cells compared with proliferating cells. Interestingly, silencing SCAMP4 in senescent fibroblasts reduced the secretion of SASP factors, including interleukin 6 (IL6), IL8, growth differentiation factor 15 (GDF-15), C-X-C motif chemokine ligand 1 (CXCL1), and IL7, while, conversely, SCAMP4 overexpression in proliferating fibroblasts increased SASP factor secretion. Our results indicate that SCAMP4 accumulates on the surface of senescent cells, promotes SASP factor secretion, and critically enhances the SASP phenotype.
journal_name
Genes Devjournal_title
Genes & developmentauthors
Kim KM,Noh JH,Bodogai M,Martindale JL,Pandey PR,Yang X,Biragyn A,Abdelmohsen K,Gorospe Mdoi
10.1101/gad.313270.118subject
Has Abstractpub_date
2018-07-01 00:00:00pages
909-914issue
13-14eissn
0890-9369issn
1549-5477pii
32/13-14/909journal_volume
32pub_type
杂志文章abstract::Epithelial-mesenchymal transition (EMT) is thought to be an important, possibly essential, component of the process of tumor dissemination and metastasis. About 20%-30% of Hras mutant mouse skin carcinomas induced by chemical initiation/promotion protocols have undergone EMT. Reduced exposure to TPA-induced chronic in...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.210427.112
更新日期:2013-03-15 00:00:00
abstract::Histone deacetylase 3 (HDAC3) is one of four members of the human class I HDACs that regulates gene expression by deacetylation of histones and nonhistone proteins. Early studies have suggested that HDAC3 activity is regulated by association with the corepressors N-CoR and SMRT. Here we demonstrate that, in addition t...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1286005
更新日期:2005-04-01 00:00:00
abstract::The embryonic expression of COUP-TFII, an orphan nuclear receptor, suggests that it may participate in mesenchymal-epithelial interactions required for organogenesis. Targeted deletion of the COUP-TFII gene results in embryonic lethality with defects in angiogenesis and heart development. COUP-TFII mutants are defecti...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.13.8.1037
更新日期:1999-04-15 00:00:00
abstract::The distal appendages (DAPs) of centrioles have been proposed to anchor cilia to the plasma membrane, but their molecular composition, assembly, and exact function in ciliogenesis remain poorly understood. Using quantitative centrosome proteomics and superresolution microscopy, we identified five DAP components, inclu...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.207043.112
更新日期:2013-01-15 00:00:00
abstract::In petunia flowers, the loci an1, an2, and an11 control the pigmentation of the flower by stimulating the transcription of anthocyanin biosynthetic genes. The an1 and an2 locus were recently cloned and encode a basic helix-loop-helix (bHLH) and MYB-domain transcriptional activator, respectively. Here, we report the is...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.11.11.1422
更新日期:1997-06-01 00:00:00
abstract::The choice of self-renewal versus differentiation is a fundamental issue in stem cell and cancer biology. Neural progenitors of the Drosophila post-embryonic brain, larval neuroblasts (NBs), divide asymmetrically in a stem cell-like fashion to generate a self-renewing NB and a Ganglion Mother Cell (GMC), which divides...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1487506
更新日期:2006-12-15 00:00:00
abstract::The td, nrdB, and sunY introns of bacteriophage T4 each contain a long open reading frame (ORF). These ORFs are preceded by functional T4 late promoters and, in the case of the nrdB intron ORF, a functional middle promoter. Expression of phage-encoded intron ORF-lacZ fusions indicates that these T4 genes are highly re...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.2.12b.1791
更新日期:1988-12-01 00:00:00
abstract::We demonstrate here that the previously described bacterial promoter upstream element (UP element) consists of two distinct subsites, each of which, by itself, can bind the RNA polymerase holoenzyme alpha subunit carboxy-terminal domain (RNAP alphaCTD) and stimulate transcription. Using binding-site-selection experime...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.13.16.2134
更新日期:1999-08-15 00:00:00
abstract::Disruption of the balanced modulation of reversible tyrosine phosphorylation has been implicated in the etiology of various human cancers, including breast cancer. Protein Tyrosine Phosphatase N23 (PTPN23) resides in chromosomal region 3p21.3, which is hemizygously or homozygously lost in some breast cancer patients. ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.304261.117
更新日期:2017-10-01 00:00:00
abstract::The visual system is a powerful model for probing the development, connectivity, and function of neural circuits. Two genetically tractable species, mice and flies, are together providing a great deal of understanding of these processes. Current efforts focus on integrating knowledge gained from three cross-fostering ...
journal_title:Genes & development
pub_type: 杂志文章,评审
doi:10.1101/gad.248245.114
更新日期:2014-12-01 00:00:00
abstract::Long understood as a bona fide tumor suppressor that safeguards the integrity of the genome via regulating numerous cellular outcomes, p53 may also exert its decisive and versatile functions by controlling DNA methylation. In this issue of Genes & Development, Tovy and colleagues (pp. 959-972) report that, in naïve mo...
journal_title:Genes & development
pub_type: 评论,杂志文章,评审
doi:10.1101/gad.302364.117
更新日期:2017-05-15 00:00:00
abstract::IkappaB kinases (IKKs) IKK1 and IKK2 are two putative IkappaBalpha kinases involved in NF-kappaB activation. To examine the in vivo functions of IKK1, we generated IKK1-deficient mice. The mutant mice are perinatally lethal and exhibit a wide range of developmental defects. Newborn mutant mice have shiny, taut, and st...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.13.10.1322
更新日期:1999-05-15 00:00:00
abstract::Studying the early stages of cancer can provide important insight into the molecular basis of the disease. We identified a preneoplastic stage in the patched (ptc) mutant mouse, a model for the brain tumor medulloblastoma. Preneoplastic cells (PNCs) are found in most ptc mutants during early adulthood, but only 15% of...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1759909
更新日期:2009-01-15 00:00:00
abstract::The P family of transposable elements in Drosophila transpose by a cut-and-paste mechanism involving double-strand gap repair. We report here that a Drosophila mutagen-sensitive mutant, mus3O9, contains a mutation in IRBP (inverted repeat binding protein), the Drosophila homolog of the mammalian Ku p70 gene. We show t...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.10.8.921
更新日期:1996-04-15 00:00:00
abstract::To find new genes that influence liver lipid mass, we performed a genetic screen for zebrafish mutants with hepatic steatosis, a pathological accumulation of fat. The red moon (rmn) mutant develops hepatic steatosis as maternally deposited yolk is depleted. Conversely, hepatic steatosis is suppressed in rmn mutants by...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.180968.111
更新日期:2012-02-01 00:00:00
abstract::Morphogen gradients of secreted molecules play critical roles in the establishment of the spatial pattern of gene expression. During midgut development in Drosophila, secreted molecules of Decapentaplegic (Dpp) and Wingless (Wg) establish unique transcriptional regulation within target cells to specify the resultant c...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.12.17.2724
更新日期:1998-09-01 00:00:00
abstract::We characterized a gene, extradenticle, which seems to interact with a specific subset of Drosophila homeo domain proteins, possibly affecting their target specificity. This interpretation is based on an examination of the zygotic and maternal effect phenotypes of extradenticle mutations. In embryos with reduced level...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.4.7.1209
更新日期:1990-07-01 00:00:00
abstract::The Wnt pathway controls numerous developmental processes via the beta-catenin-TCF/LEF transcription complex. Deregulation of the pathway results in the aberrant accumulation of beta-catenin in the nucleus, often leading to cancer. Normally, cytoplasmic beta-catenin associates with APC and axin and is continuously pho...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.230302
更新日期:2002-05-01 00:00:00
abstract::The Brr2 helicase provides the key remodeling activity for spliceosome catalytic activation, during which it disrupts the U4/U6 di-snRNP (small nuclear RNA protein), and its activity has to be tightly regulated. Brr2 exhibits an unusual architecture, including an ∼ 500-residue N-terminal region, whose functions and mo...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.271528.115
更新日期:2015-12-15 00:00:00
abstract::In this issue of Genes & Development, Wierzbicki and colleagues (pp. 1825-1836) examine the current model of RNA-directed DNA methylation (RdDM) by determining genome-wide distributions of RNA polymerase V (Pol V) occupancy, siRNAs, and DNA methylation. Their data support the key role of base-pairing between Pol V tra...
journal_title:Genes & development
pub_type: 评论,杂志文章
doi:10.1101/gad.200410.112
更新日期:2012-08-15 00:00:00
abstract::Neurofibromatosis type 1 (NF1) is a prevalent genetic disorder that affects growth properties of neural-crest-derived cell populations. In addition, approximately one-half of NF1 patients exhibit learning disabilities. To characterize NF1 function both in vitro and in vivo, we circumvent the embryonic lethality of NF1...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.862101
更新日期:2001-04-01 00:00:00
abstract::Sex determination is regulated by diverse pathways. Although upstream signals vary, a cysteine-rich DNA-binding domain (the DM motif) is conserved within downstream transcription factors of Drosophila melanogaster (Doublesex) and Caenorhabditis elegans (MAB-3). Vertebrate DM genes have likewise been identified and, re...
journal_title:Genes & development
pub_type: 杂志文章
doi:
更新日期:2000-07-15 00:00:00
abstract::A new gene, SCH9, was isolated from Saccharomyces cerevisiae by its ability to complement a cdc25ts mutation. Sequence analysis indicates that it encodes a 90,000-dalton protein with a carboxy-terminal domain homologous to yeast and mammalian cAMP-dependent protein kinase catalytic subunits. In addition to suppressing...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.2.5.517
更新日期:1988-05-01 00:00:00
abstract::The Wnt signaling cascade is a central regulator of cell fate determination during embryonic development, whose deregulation contributes to oncogenesis. Naked cuticle is the first Wnt-induced antagonist found in this pathway, establishing a negative-feedback loop that limits the Wnt signal required for early segmentat...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.328905
更新日期:2005-02-01 00:00:00
abstract::The ability to initiate organs throughout the lifecycle is a unique feature of plant development that is executed by groups of stem cells called meristems. The balance between stem cell proliferation and organ initiation is carefully regulated and ensures that organs can be initiated in regular geometric patterns. To ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.208501
更新日期:2001-10-15 00:00:00
abstract::To define the functional pathways regulating epithelial cell migration, we performed a genome-wide RNAi screen using 55,000 pooled lentiviral shRNAs targeting ∼11,000 genes, selecting for transduced cells with increased motility. A stringent validation protocol generated a set of 31 genes representing diverse pathways...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1989110
更新日期:2010-12-01 00:00:00
abstract::Direct reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) provides a unique opportunity to derive patient-specific stem cells with potential applications in tissue replacement therapies and without the ethical concerns of human embryonic stem cells (hESCs). However, cellular senescence, which c...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.173922.111
更新日期:2011-11-01 00:00:00
abstract::Extensive DNA elimination via a DNA breakage and rejoining process occurs during macronuclear development in the hypotrich ciliate Euplotes crassus. The excision process involves the removal of short, unique segments of DNA (internal eliminated sequences; IESs) and at least two highly repetitive families of transposon...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.7.1.84
更新日期:1993-01-01 00:00:00
abstract::We generated and characterized greater than 500 Drosophila strains that carry single copies of a novel P-element enhancer detector. In the majority of the strains, the beta-galactosidase reporter gene in the P-transposon responds to nearby transcriptional regulatory sequences in the genome. A remarkable diversity of s...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.3.9.1288
更新日期:1989-09-01 00:00:00
abstract::Codon usage bias is a universal feature of all genomes, but its in vivo biological functions in animal systems are not clear. To investigate the in vivo role of codon usage in animals, we took advantage of the sensitivity and robustness of the Drosophila circadian system. By codon-optimizing parts of Drosophila period...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.281030.116
更新日期:2016-08-01 00:00:00