Abstract:
:Introduction of simian virus 40 T antigen into rodent fibroblasts gives rise to cells that can proliferate indefinitely but are dependent upon it for maintenance of their growth once the normal mitotic life span has elapsed. Inactivation of T antigen in these immortalized cells causes rapid and irreversible cessation of growth. To determine whether this growth arrest is associated with entry into senescence, we have undertaken a genetic and biological analysis of conditionally immortal (tsa) cell lines derived by immortalizing rat embryo fibroblasts with the thermolabile tsA58 T antigen. This analysis has identified the following parallels between the tsa cells after inactivation of T antigen and senescent rat embryo fibroblasts: (i) growth arrest is irreversible; (ii) it occurs in G1 as well as G2; (iii) the G1 block can be partially overcome by stimulation with 20% fetal calf serum, but the G2 block cannot be overcome; (iv) 20% fetal calf serum induces c-fos, but c-myc is unaltered; and (v) fibronectin and p21(Waf1/Cip1/Sdi1) are upregulated upon growth arrest. These results suggest that T-antigen-immortalized fibroblasts are committed to undergo senescence but are prevented from undergoing this process by T antigen. Inactivation of T antigen removes this block and results in senescence of the cells. Thus, these cell lines may represent a powerful system for study of the molecular basis of entry into senescence.
journal_name
Mol Cell Bioljournal_title
Molecular and cellular biologyauthors
Gonos ES,Burns JS,Mazars GR,Kobrna A,Riley TE,Barnett SC,Zafarana G,Ludwig RL,Ikram Z,Powell AJ,Jat PSdoi
10.1128/mcb.16.9.5127subject
Has Abstractpub_date
1996-09-01 00:00:00pages
5127-38issue
9eissn
0270-7306issn
1098-5549journal_volume
16pub_type
杂志文章abstract::Unintended DNA rearrangements in a differentiating lymphocyte can have severe, oncogenic consequences, but the mechanisms for avoiding pathogenic outcomes in V(D)J recombination are not well understood. The first level at which fidelity is instituted is in discrimination by the recombination proteins between authentic...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.20.14.5032-5040.2000
更新日期:2000-07-01 00:00:00
abstract::Analysis of the p50 and p65 subunits of the NF-kappa B transcription factor complex has revealed that both proteins can interact with related DNA sequences through either homo- or heterodimer formation. In addition, the product of the proto-oncogene c-rel can bind to similar DNA motifs by itself or as a heterodimer wi...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.12.10.4412
更新日期:1992-10-01 00:00:00
abstract::Mutations in the spin gene are characterized by an extraordinarily strong rejection behavior of female flies in response to male courtship. They are also accompanied by decreases in the viability, adult life span, and oviposition rate of the flies. In spin mutants, some oocytes and adult neural cells undergo degenerat...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.21.11.3775-3788.2001
更新日期:2001-06-01 00:00:00
abstract::Recognition of gene promoters by RNA polymerase II is mediated by general transcription factor IID (TFIID), which has been thought to be a static complex and to play a passive role in the regulation of gene expression under the instruction of gene-specific transcription factors. Here we show that transforming growth f...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00449-17
更新日期:2018-02-12 00:00:00
abstract::In Caenorhabditis elegans, the central cell-killing process is essentially controlled by the interplay of four apoptotic factors: EGL-1/BH3-only protein, CED-9/Bcl2, CED-4/Apaf1, and CED-3/caspase. In cells destined to die, EGL-1 binds to CED-9 and results in the release of CED-4 from the mitochondrion-tethered CED-9-...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.01509-08
更新日期:2009-07-01 00:00:00
abstract::In the mouse mammary tumor virus promoter, a tandem of octamer motifs, recognized by ubiquitous and tissue-restricted Oct transcription factors, is located upstream of the TATA box and next to a binding site for the transcription factor nuclear factor I (NF-I). Their function was investigated with mutant long terminal...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.14.2.1191
更新日期:1994-02-01 00:00:00
abstract::Temporal analysis of DNA replication and histone mRNA accumulation in a hamster fibroblast cell cycle mutant (K12) showed that histone mRNA accumulates periodically during the cell cycle and reaches its highest level in the S phase. The direct correlation between the initiation of DNA synthesis and the accumulation of...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.4.11.2364
更新日期:1984-11-01 00:00:00
abstract::In the sea urchin embryo, late histone genes are transcribed at low levels during cleavage and blastula formation and at substantially higher levels in later stages of embryogenesis. To investigate the molecular basis of the stage-specific expression of a late H2B histone gene, we injected mutant genes lacking portion...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.10.12.6730
更新日期:1990-12-01 00:00:00
abstract::The use of small-molecule inhibitors to study molecular components of cellular signal transduction pathways provides a means of analysis complementary to currently used techniques, such as antisense, dominant-negative (interfering) mutants and constitutively activated mutants. We have identified and characterized a sm...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.20.23.9018-9027.2000
更新日期:2000-12-01 00:00:00
abstract::We have recently reported that the yeast chromatin-remodeling factor Swi1 can exist as a prion, [SWI(+)], demonstrating a link between prionogenesis and global transcriptional regulation. To shed light on how the Swi1 conformational switch influences Swi1 function and to define the sequence and structural requirements...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00225-10
更新日期:2010-10-01 00:00:00
abstract::Expression of the anaphase-promoting complex/cyclosome (APC/C) inhibitor Emi1 is required for the accumulation of APC/C substrates crucial for DNA synthesis and mitotic entry. We show that in vivo Emi1 expression correlates with the proliferative status of the cellular compartment and that cells lacking Emi1 undergo c...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00908-07
更新日期:2007-11-01 00:00:00
abstract::Epidermal growth factor (EGF) induces tyrosine phosphorylation of the Shc adapter protein, which plays an important role in EGF-stimulated mitogenesis. Shc stimulates Ras/mitogen-activated protein kinase (MAPK) through forming a complex with Grb2 at the phosphorylated tyrosine (Y) residue 317. In this study, we identi...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.17.4.1824
更新日期:1997-04-01 00:00:00
abstract::The levels of molecular chaperones and folding enzymes in the endoplasmic reticulum (ER) are controlled by a transcriptional induction process termed the unfolded protein response (UPR). The mammalian UPR is mediated by the cis-acting ER stress response element (ERSE), the consensus sequence of which is CCAAT-N(9)-CCA...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.21.4.1239-1248.2001
更新日期:2001-02-01 00:00:00
abstract::The recruitment of transcriptional coactivators, including histone modifying enzymes, is an important step in transcription regulation. A typical activator is thought to interact with several cofactors, presumably in a sequential manner. The common use of several cofactors raises the question of how activators achieve...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.01461-07
更新日期:2008-04-01 00:00:00
abstract::The recombinant shuttle vector pSV2gpt was introduced into V79 Chinese hamster cells, and stable transformants expressing the Escherichia coli gpt gene were selected. Two transformants carrying tandem duplications of the plasmid at a single site were identified and fused to simian COS-1 cells. Plasmid DNA recovered fr...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.4.11.2266
更新日期:1984-11-01 00:00:00
abstract::The functional importance of the two clusters of positively charged amino acids which flank the hydrophobic membrane-anchoring sequence of polyomavirus middle T (mT) protein has been investigated by using site-directed mutagenesis. A clear asymmetry was apparent. No effect on transformation was seen following multiple...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.12.11.5050
更新日期:1992-11-01 00:00:00
abstract::The int-1 proto-oncogene is a target for insertional activation of transcription by mouse mammary tumor virus in many murine mammary tumors. Whereas no expression of int-1 is seen in normal mammary tissue, int-1 RNA can be detected in normal mice in the neural tubes of midgestation embryos and in postmeiotic spermatoc...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.9.8.3377
更新日期:1989-08-01 00:00:00
abstract::Using several actin isotype-specific cDNA probes, we found actin mRNA of two size classes, 2.1 and 1.5 kilobases (kb), in extracts of polyadenylated and nonpolyadenylated RNA from sexually mature CD-1 mouse testes. Although the 2.1-kb sequence was present in both meiotic and postmeiotic testicular cell types, it decre...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.5.7.1649
更新日期:1985-07-01 00:00:00
abstract::Phosphorylation of eukaryotic initiation factor 2α (eIF2α) controls transcriptome-wide changes in mRNA translation in stressed cells. While phosphorylated eIF2α (P-eIF2α) attenuates global protein synthesis, mRNAs encoding stress proteins are more efficiently translated. Two eIF2α phosphatases, containing GADD34 and C...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00190-16
更新日期:2016-06-15 00:00:00
abstract::Mammalian Ras GTPase-activating protein (GAP), p120 Ras-GAP, has been implicated as both a downregulator and effector of Ras proteins, but its precise role in Ras-mediated signal transduction pathways is unclear. To begin a genetic analysis of the role of p120 Ras-GAP we identified a homolog from the fruit fly Drosoph...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.19.3.1928
更新日期:1999-03-01 00:00:00
abstract::Ikaros (Ik) is a critical regulator of hematopoietic gene expression. Here, we established that the Ik interactions with GATA transcription factors and cyclin-dependent kinase 9 (Cdk9), a component of the positive transcription elongation factor b (P-TEFb), are required for transcriptional activation of Ik target gene...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00296-13
更新日期:2013-08-01 00:00:00
abstract::Furin is a subtilisin-related endoprotease which processes a wide range of bioactive proteins. Furin is concentrated in the trans-Golgi network (TGN), where proteolytic activation of many precursor proteins takes place. A significant fraction of furin, however, cycles among the TGN, the plasma membrane, and endosomes,...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.19.4.3136
更新日期:1999-04-01 00:00:00
abstract::Human CRK protein is a homolog of the chicken v-crk oncogene product and consists mostly of src homology region 2 (SH2) and SH3, which are shared by many proteins, in particular those involved in signal transduction. SH2 has been shown to bind specifically to phosphotyrosine-containing peptides. We report here that bo...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.13.7.4409
更新日期:1993-07-01 00:00:00
abstract::The gene encoding the SNF5/Ini1 core subunit of the SWI/SNF chromatin remodeling complex is a tumor suppressor in humans and mice, with an essential role in early embryonic development. To investigate further the function of this gene, we have generated a Cre/lox-conditional mouse line. We demonstrate that Snf5 deleti...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.26.7.2661-2674.2006
更新日期:2006-04-01 00:00:00
abstract::Human cells lacking functional p53 exhibit a partial deficiency in nucleotide excision repair (NER), the pathway for repair of UV-induced DNA damage. The global genomic repair (GGR) subpathway of NER, but not transcription-coupled repair (TCR), is mainly affected by p53 loss or inactivation. We have utilized mouse emb...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.20.10.3705-3714.2000
更新日期:2000-05-01 00:00:00
abstract::Posttranscriptional regulation is important for tumor necrosis factor alpha (TNF-alpha) expression in monocytes and macrophages, and an AU-rich element (ARE) in the 3' untranslated region (UTR) of TNF-alpha mRNA is implicated in control of its translation and mRNA stability. Regulation of mRNA turnover is thought to b...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.21.3.721-730.2001
更新日期:2001-02-01 00:00:00
abstract::Progression through mitosis requires the inactivation of the protein kinase activity of the p34cdc2-cyclin complex by a mechanism involving the degradation of cyclin. We have examined the stability in Xenopus egg extracts of radiolabeled Xenopus or sea urchin B-type cyclins synthesized in reticulocyte lysates. Xenopus...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.13.3.1480
更新日期:1993-03-01 00:00:00
abstract::The cell cycle-regulatory transcription factor E2F-1 is regulated by interactions with proteins such as the retinoblastoma gene product and by cell cycle-dependent alterations in E2F-1 mRNA abundance. To better understand this latter phenomenon, we have isolated the human E2F-1 promoter. The human E2F-1 promoter, fuse...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.14.10.6607
更新日期:1994-10-01 00:00:00
abstract::Menin, the product of the multiple endocrine neoplasia type I gene, has been implicated in several biological processes, including the control of gene expression and apoptosis, the modulation of mitogen-activated protein kinase pathways, and DNA damage sensing or repair. In this study, we have investigated the functio...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.25.22.9960-9972.2005
更新日期:2005-11-01 00:00:00
abstract::BUD23 was identified from a bioinformatics analysis of Saccharomyces cerevisiae genes involved in ribosome biogenesis. Deletion of BUD23 leads to severely impaired growth, reduced levels of the small (40S) ribosomal subunit, and a block in processing 20S rRNA to 18S rRNA, a late step in 40S maturation. Bud23 belongs t...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.01674-07
更新日期:2008-05-01 00:00:00