RB-dependent S-phase response to DNA damage.

Abstract:

:The retinoblastoma tumor suppressor protein (RB) is a potent inhibitor of cell proliferation. RB is expressed throughout the cell cycle, but its antiproliferative activity is neutralized by phosphorylation during the G(1)/S transition. RB plays an essential role in the G(1) arrest induced by a variety of growth inhibitory signals. In this report, RB is shown to also be required for an intra-S-phase response to DNA damage. Treatment with cisplatin, etoposide, or mitomycin C inhibited S-phase progression in Rb(+/+) but not in Rb(-/-) mouse embryo fibroblasts. Dephosphorylation of RB in S-phase cells temporally preceded the inhibition of DNA synthesis. This S-phase dephosphorylation of RB and subsequent inhibition of DNA replication was observed in p21(Cip1)-deficient cells. The induction of the RB-dependent intra-S-phase arrest persisted for days and correlated with a protection against DNA damage-induced cell death. These results demonstrate that RB plays a protective role in response to genotoxic stress by inhibiting cell cycle progression in G(1) and in S phase.

journal_name

Mol Cell Biol

authors

Knudsen KE,Booth D,Naderi S,Sever-Chroneos Z,Fribourg AF,Hunton IC,Feramisco JR,Wang JY,Knudsen ES

doi

10.1128/mcb.20.20.7751-7763.2000

subject

Has Abstract

pub_date

2000-10-01 00:00:00

pages

7751-63

issue

20

eissn

0270-7306

issn

1098-5549

journal_volume

20

pub_type

杂志文章
  • Assembly of 60S ribosomal subunits is perturbed in temperature-sensitive yeast mutants defective in ribosomal protein L16.

    abstract::Temperature-sensitive mutants defective in 60S ribosomal subunit protein L16 of Saccharomyces cerevisiae were isolated through hydroxylamine mutagenesis of the RPL16B gene and plasmid shuffling. Two heat-sensitive and two cold-sensitive isolates were characterized. The growth of the four mutants is inhibited at their ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.11.11.5681

    authors: Moritz M,Pulaski BA,Woolford JL Jr

    更新日期:1991-11-01 00:00:00

  • Phospholipase Cgamma2 contributes to light-chain gene activation and receptor editing.

    abstract::Phospholipase Cgamma2 (PLCgamma2) is critical for pre-B-cell receptor (pre-BCR) and BCR signaling. Current studies discovered that PLCgamma2-deficient mice had reduced immunoglobulin lambda (Iglambda) light-chain usage throughout B-cell maturation stages, including transitional type 1 (T1), transitional type 2 (T2), a...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.02273-06

    authors: Bai L,Chen Y,He Y,Dai X,Lin X,Wen R,Wang D

    更新日期:2007-09-01 00:00:00

  • Sex-lethal autoregulation requires multiple cis-acting elements upstream and downstream of the male exon and appears to depend largely on controlling the use of the male exon 5' splice site.

    abstract::The on/off state of the binary switch gene Sex-lethal (Sxl), which controls somatic sexual development in Drosophila melanogaster, is regulated at the level of alternative splicing. In males, in which the gene is off, the default splicing machinery produces nonfunctional mRNAs; in females, in which the gene is on, the...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.13.12.7734

    authors: Horabin JI,Schedl P

    更新日期:1993-12-01 00:00:00

  • Transcription factor GATA-4 regulates cardiac muscle-specific expression of the alpha-myosin heavy-chain gene.

    abstract::The alpha-myosin heavy-chain (alpha-MHC) gene is the major structural protein in the adult rodent myocardium. Its expression is restricted to the heart by a complex interplay of trans-acting factors and their cis-acting sites. However, to date, the factors that have been shown to regulate expression of this gene have ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.14.7.4947

    authors: Molkentin JD,Kalvakolanu DV,Markham BE

    更新日期:1994-07-01 00:00:00

  • Association with Ets-1 causes ligand- and AF2-independent activation of nuclear receptors.

    abstract::The vitamin D receptor (VDR) normally functions as a ligand-dependent transcriptional activator. Here we show that, in the presence of Ets-1, VDR stimulates the prolactin promoter in a ligand-independent manner, behaving as a constitutive activator. Mutations in the AF2 domain abolish vitamin D-dependent transactivati...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.20.23.8793-8802.2000

    authors: Tolón RM,Castillo AI,Jiménez-Lara AM,Aranda A

    更新日期:2000-12-01 00:00:00

  • Role of the liver-enriched transcription factor hepatocyte nuclear factor 1 in transcriptional regulation of the factor V111 gene.

    abstract::Coagulation factor VIII is an essential cofactor required for normal hemostatic function. A deficiency in factor VIII results in the bleeding disorder hemophilia A. Despite the fact that the factor VIII gene was cloned a decade ago, the mechanisms which control its transcription remain unresolved. In our studies, we h...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.16.5.1936

    authors: McGlynn LK,Mueller CR,Begbie M,Notley CR,Lillicrap D

    更新日期:1996-05-01 00:00:00

  • Characterization of Sleeping Beauty transposition and its application to genetic screening in mice.

    abstract::The use of mutant mice plays a pivotal role in determining the function of genes, and the recently reported germ line transposition of the Sleeping Beauty (SB) transposon would provide a novel system to facilitate this approach. In this study, we characterized SB transposition in the mouse germ line and assessed its p...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.23.24.9189-9207.2003

    authors: Horie K,Yusa K,Yae K,Odajima J,Fischer SE,Keng VW,Hayakawa T,Mizuno S,Kondoh G,Ijiri T,Matsuda Y,Plasterk RH,Takeda J

    更新日期:2003-12-01 00:00:00

  • Influence of the RNA-binding protein HuR in pVHL-regulated p53 expression in renal carcinoma cells.

    abstract::A recent analysis of gene expression in renal cell carcinoma cells led to the identification of mRNAs whose translation was dependent on the presence of the von Hippel-Lindau (VHL) tumor suppressor gene product, pVHL. Here, we investigate the finding that pVHL-expressing RCC cells (VHL(+)) exhibited elevated levels of...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.23.20.7083-7095.2003

    authors: Galbán S,Martindale JL,Mazan-Mamczarz K,López de Silanes I,Fan J,Wang W,Decker J,Gorospe M

    更新日期:2003-10-01 00:00:00

  • A novel c-fgr exon utilized in Epstein-Barr virus-infected B lymphocytes but not in normal monocytes.

    abstract::The fgr proto-oncogene encodes a nonreceptor protein-tyrosine kinase, designated p55c-fgr. In this study, we have isolated human fgr cDNA molecules from normal monocyte mRNA templates. Nucleotide sequence analysis of the longest fgr cDNA revealed a 5' untranslated region of 927 bp which included two Alu-like repeats a...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.11.3.1500

    authors: Gutkind JS,Link DC,Katamine S,Lacal P,Miki T,Ley TJ,Robbins KC

    更新日期:1991-03-01 00:00:00

  • The alternatively spliced exon of the platelet-derived growth factor A chain encodes a nuclear targeting signal.

    abstract::We have previously shown that the SIS/platelet-derived growth factor B chain contains a nuclear targeting signal near its C terminus. Here we show that the platelet-derived growth factor A chain also contains a nuclear targeting signal encoded by an exon which is subject to alternative splicing. This sequence is capab...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.9.5.2251

    authors: Maher DW,Lee BA,Donoghue DJ

    更新日期:1989-05-01 00:00:00

  • Transformation by v-myb correlates with trans-activation of gene expression.

    abstract::The v-myb oncogene of avian myeloblastosis virus causes acute myelomonocytic leukemia in chickens and transforms avian myeloid cells in vitro. Its protein product p48v-myb is a nuclear, sequence-specific, DNA-binding protein which activates gene expression in transient DNA transfection studies. To investigate the rela...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.10.6.2591

    authors: Lane T,Ibanez C,Garcia A,Graf T,Lipsick J

    更新日期:1990-06-01 00:00:00

  • Structure and transforming potential of the human cot oncogene encoding a putative protein kinase.

    abstract::A new transforming gene has been molecularly cloned from hamster SHOK cells transformed with DNA extracted from a human thyroid carcinoma cell line and named the cot (cancer Osaka thyroid) oncogene. cDNA sequencing disclosed that this oncogene codes for a protein with 415 amino acid residues, and computer matching sho...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.11.8.4088

    authors: Miyoshi J,Higashi T,Mukai H,Ohuchi T,Kakunaga T

    更新日期:1991-08-01 00:00:00

  • Jun is phosphorylated by several protein kinases at the same sites that are modified in serum-stimulated fibroblasts.

    abstract::c-jun is a member of the family of immediate-early genes whose expression is induced by factors such as serum stimulation, phorbol ester, and differentiation signals. Here we show that increased Jun synthesis after serum stimulation is accompanied by a concomitant increase in phosphorylation. Several serine-threonine ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.12.10.4694

    authors: Baker SJ,Kerppola TK,Luk D,Vandenberg MT,Marshak DR,Curran T,Abate C

    更新日期:1992-10-01 00:00:00

  • GATA and Ets cis-acting sequences mediate megakaryocyte-specific expression.

    abstract::The human glycoprotein IIB (GPIIB) gene is expressed only in megakaryocytes, and its promoter displays cell type specificity. We show that this specificity involved two cis-acting sequences. The first one, located at -55, contains a GATA binding site. Point mutations that abolish protein binding on this site decrease ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.13.1.668

    authors: Lemarchandel V,Ghysdael J,Mignotte V,Rahuel C,Roméo PH

    更新日期:1993-01-01 00:00:00

  • Embryonic lethality, decreased erythropoiesis, and defective octamer-dependent promoter activation in Oct-1-deficient mice.

    abstract::Oct-1 is a sequence-specific DNA binding transcription factor that is believed to regulate a large group of tissue-specific and ubiquitous genes. Both Oct-1 and the related but tissue-restricted Oct-2 protein bind to a DNA sequence termed the octamer motif (5'-ATGCAAAT-3') with equal affinity in vitro. To address the ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.24.3.1022-1032.2004

    authors: Wang VE,Schmidt T,Chen J,Sharp PA,Tantin D

    更新日期:2004-02-01 00:00:00

  • P-element-induced interallelic gene conversion of insertions and deletions in Drosophila melanogaster.

    abstract::We studied the process by which whd, a P-element insertion allele of the Drosophila melanogaster white locus, is replaced by its homolog in the presence of transposase. These events are interpreted as the result of double-strand gap repair following excision of the P transposon in whd. We used a series of alleles deri...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.13.11.7006

    authors: Johnson-Schlitz DM,Engels WR

    更新日期:1993-11-01 00:00:00

  • Inhibition of chicken embryo lens differentiation and lens junction formation in culture by pp60v-src.

    abstract::A culture system was developed which permitted the differentiation of chicken lens epithelial cells to lentoid bodies which contained several cell layers, accumulated high levels of delta-crystallin, and produced extensive gap junctions. This differentiation process was prevented when the cells were infected with a te...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.8.4.1414

    authors: Menko AS,Boettiger D

    更新日期:1988-04-01 00:00:00

  • Yap, a novel family of eight bZIP proteins in Saccharomyces cerevisiae with distinct biological functions.

    abstract::Saccharomyces cerevisiae contains eight members of a novel and fungus-specific family of bZIP proteins that is defined by four atypical residues on the DNA-binding surface. Two of these proteins, Yap1 and Yap2, are transcriptional activators involved in pleiotropic drug resistance. Although initially described as AP-1...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.17.12.6982

    authors: Fernandes L,Rodrigues-Pousada C,Struhl K

    更新日期:1997-12-01 00:00:00

  • Fal1p is an essential DEAD-box protein involved in 40S-ribosomal-subunit biogenesis in Saccharomyces cerevisiae.

    abstract::A previously uncharacterized Saccharomyces cerevisiae gene, FAL1, was found by sequence comparison as a homolog of the eukaryotic translation initiation factor 4A (eIF4A). Fal1p has 55% identity and 73% similarity on the amino acid level to yeast eIF4A, the prototype of ATP-dependent RNA helicases of the DEAD-box prot...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.17.12.7283

    authors: Kressler D,de la Cruz J,Rojo M,Linder P

    更新日期:1997-12-01 00:00:00

  • Membrane localization of phosphatidylinositol 3-kinase is sufficient to activate multiple signal-transducing kinase pathways.

    abstract::Phosphatidylinositol (PI) 3-kinase is a cytoplasmic signaling molecule recruited to the membrane by activated growth factor receptors. The p85 subunit of PI 3-kinase links the catalytic p110 subunit to activated growth factor receptors and is required for enzymatic activity of p110. In this report, we describe the eff...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.16.8.4117

    authors: Klippel A,Reinhard C,Kavanaugh WM,Apell G,Escobedo MA,Williams LT

    更新日期:1996-08-01 00:00:00

  • Cyclin-dependent kinase 1-mediated Bcl-xL/Bcl-2 phosphorylation acts as a functional link coupling mitotic arrest and apoptosis.

    abstract::Despite detailed knowledge of the components of the spindle assembly checkpoint, a molecular explanation of how cells die after prolonged spindle checkpoint activation, and thus how microtubule inhibitors and other antimitotic drugs ultimately elicit their lethal effects, has yet to emerge. Mitotically arrested cells ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.00882-09

    authors: Terrano DT,Upreti M,Chambers TC

    更新日期:2010-02-01 00:00:00

  • Canonical Notch signaling is dispensable for early cell fate specifications in mammals.

    abstract::The canonical Notch signaling pathway mediated by Delta- and Jagged-like Notch ligands determines a variety of cell fates in metazoa. In Caenorhabditis elegans and sea urchins, canonical Notch signaling is essential for different cell fate specifications during early embryogenesis or the formation of endoderm, mesoder...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.25.21.9503-9508.2005

    authors: Shi S,Stahl M,Lu L,Stanley P

    更新日期:2005-11-01 00:00:00

  • An intronic locus control region plays an essential role in the establishment of an autonomous hepatic chromatin domain for the human vitamin D-binding protein gene.

    abstract::The human vitamin D-binding protein (hDBP) gene exists in a cluster of four liver-expressed genes. A minimal hDBP transgene, containing a defined set of liver-specific DNase I hypersensitive sites (HSs), is robustly expressed in mouse liver in a copy-number-dependent manner. Here we evaluate these HSs for function. De...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.00331-07

    authors: Hiroki T,Liebhaber SA,Cooke NE

    更新日期:2007-11-01 00:00:00

  • The poly(A) tail inhibits the assembly of a 3'-to-5' exonuclease in an in vitro RNA stability system.

    abstract::We have developed an in vitro system which faithfully reproduces several aspects of general mRNA stability. Poly(A)- RNAs were rapidly and efficiently degraded in this system with no detectable intermediates by a highly processive 3'-to-5' exonuclease activity. The addition of a poly(A) tail of at least 30 bases, or a...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.17.1.398

    authors: Ford LP,Bagga PS,Wilusz J

    更新日期:1997-01-01 00:00:00

  • Multiple functional elements comprise a Mammalian chromosomal replicator.

    abstract::The structure of replication origins in metazoans is only nominally similar to that in model organisms, such as Saccharomyces cerevisiae. By contrast to the compact origins of budding yeast, in metazoans multiple elements act as replication start sites or control replication efficiency. We first reported that replicat...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.23.5.1832-1842.2003

    authors: Liu G,Malott M,Leffak M

    更新日期:2003-03-01 00:00:00

  • Role of the 3' splice site in U12-dependent intron splicing.

    abstract::U12-dependent introns containing alterations of the 3' splice site AC dinucleotide or alterations in the spacing between the branch site and the 3' splice site were examined for their effects on splice site selection in vivo and in vitro. Using an intron with a 5' splice site AU dinucleotide, any nucleotide could serv...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.21.6.1942-1952.2001

    authors: Dietrich RC,Peris MJ,Seyboldt AS,Padgett RA

    更新日期:2001-03-01 00:00:00

  • The novel primary response gene MyD118 and the proto-oncogenes myb, myc, and bcl-2 modulate transforming growth factor beta 1-induced apoptosis of myeloid leukemia cells.

    abstract::Cell numbers are regulated by a balance among proliferation, growth arrest, and programmed cell death. A profound example of cell homeostasis, controlled throughout life, is the complex process of blood cell development, yet little is understood about the intracellular mechanisms that regulate blood cell growth arrest...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.14.4.2352

    authors: Selvakumaran M,Lin HK,Sjin RT,Reed JC,Liebermann DA,Hoffman B

    更新日期:1994-04-01 00:00:00

  • The Drosophila homolog of mammalian zinc finger factor MTF-1 activates transcription in response to heavy metals.

    abstract::Metallothioneins (MTs) are short, cysteine-rich proteins for heavy metal homeostasis and detoxification; they bind a variety of heavy metals and also act as radical scavengers. Transcription of mammalian MT genes is activated by heavy metal load via the metal-responsive transcription factor 1 (MTF-1), an essential zin...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.21.14.4505-4514.2001

    authors: Zhang B,Egli D,Georgiev O,Schaffner W

    更新日期:2001-07-01 00:00:00

  • Transcriptional activity of neural retina leucine zipper (Nrl) is regulated by c-Jun N-terminal kinase and Tip60 during retina development.

    abstract::Neural retina leucine zipper (Nrl), a key basic motif leucine zipper (bZIP) transcription factor, modulates rod photoreceptor differentiation by activating rod-specific target genes. In searching for factors that might couple with Nrl to modulate its transcriptional activity through posttranslational modification, we ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.06440-11

    authors: Kim JW,Jang SM,Kim CH,An JH,Choi KH

    更新日期:2012-05-01 00:00:00

  • A discrete region centered 22 base pairs upstream of the initiation site modulates transcription of Drosophila tRNAAsn genes.

    abstract::We have studied the mechanism by which 5'-flanking sequences modulate the in vitro transcription of eucaryotic tRNA genes. Using deletion and linker substitution mutagenesis, we have found that the 5'-flanking sequences responsible for the different in vitro transcription levels of three Drosophila tRNA5Asn genes are ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.8.10.4441

    authors: Lofquist AK,Garcia AD,Sharp SJ

    更新日期:1988-10-01 00:00:00