RB-dependent S-phase response to DNA damage.


: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.


Mol Cell Biol


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




Has Abstract


2000-10-01 00:00:00












  • Phosphorylation of SAF-A/hnRNP-U Serine 59 by Polo-Like Kinase 1 Is Required for Mitosis.

    abstract::Scaffold attachment factor A (SAF-A), also called heterogenous nuclear ribonuclear protein U (hnRNP-U), is phosphorylated on serine 59 by the DNA-dependent protein kinase (DNA-PK) in response to DNA damage. Since SAF-A, DNA-PK catalytic subunit (DNA-PKcs), and protein phosphatase 6 (PP6), which interacts with DNA-PKcs...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Douglas P,Ye R,Morrice N,Britton S,Trinkle-Mulcahy L,Lees-Miller SP

    更新日期:2015-08-01 00:00:00

  • Induction of neuronal differentiation in PC12 cells by B-cell stimulatory factor 2/interleukin 6.

    abstract::B-cell stimulatory factor 2 (BSF-2) is a lymphokine which induces the final maturation of B cells. BSF-2 acts on a variety of cells other than B cells, and moreover, expression of BSF-2 mRNA is detected in interleukin-1 beta-stimulated glioblastoma and astrocytoma cell lines. Here, we studied the function of BSF-2 on ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Satoh T,Nakamura S,Taga T,Matsuda T,Hirano T,Kishimoto T,Kaziro Y

    更新日期:1988-08-01 00:00:00

  • The transforming Rho family GTPase Wrch-1 disrupts epithelial cell tight junctions and epithelial morphogenesis.

    abstract::Wrch-1, an atypical and transforming Rho GTPase, regulates cellular activities including proliferation and actin organization, but its functions and effectors remain poorly characterized. We show here that Wrch-1 distributes along the apical and basolateral membranes in MDCK cells and binds the cell polarity protein P...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Brady DC,Alan JK,Madigan JP,Fanning AS,Cox AD

    更新日期:2009-02-01 00:00:00

  • Evolutionary conservation and predicted structure of the Drosophila extra sex combs repressor protein.

    abstract::The Drosophila extra sex combs (esc) protein, a member of the Polycomb group (PcG), is a transcriptional repressor of homeotic genes. Genetic studies have shown that esc protein is required in early embryos at about the time that other PcG proteins become engaged in homeotic gene repression. The esc protein consists p...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Ng J,Li R,Morgan K,Simon J

    更新日期:1997-11-01 00:00:00

  • Host species specificity of polyomavirus DNA replication is not altered by simian virus 40 72-base-pair repeats.

    abstract::The simian virus 40 72-base-pair repeats substituted for the polyomavirus enhancer, allowing replication and transcription in mouse 3T6 but not monkey CV-1 cells. A polyomavirus genome containing the entire simian virus 40 control region replicated at low levels in 3T6 and CV-1 cells; however, transcripts were detecte...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Campbell BA,Villarreal LP

    更新日期:1985-06-01 00:00:00

  • Yeast Upf proteins required for RNA surveillance affect global expression of the yeast transcriptome.

    abstract::mRNAs are monitored for errors in gene expression by RNA surveillance, in which mRNAs that cannot be fully translated are degraded by the nonsense-mediated mRNA decay pathway (NMD). RNA surveillance ensures that potentially deleterious truncated proteins are seldom made. NMD pathways that promote surveillance have bee...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Lelivelt MJ,Culbertson MR

    更新日期:1999-10-01 00:00:00

  • Transforming growth factor beta 1-responsive element: closely associated binding sites for USF and CCAAT-binding transcription factor-nuclear factor I in the type 1 plasminogen activator inhibitor gene.

    abstract::Transforming growth factor beta (TGF-beta) is the name of a group of closely related polypeptides characterized by a multiplicity of effects, including regulation of extracellular proteolysis and turnover of the extracellular matrix. Its cellular mechanism of action is largely unknown. TGF-beta 1 is a strong and fast ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Riccio A,Pedone PV,Lund LR,Olesen T,Olsen HS,Andreasen PA

    更新日期:1992-04-01 00:00:00

  • rme1 Mutation of Saccharomyces cerevisiae: map position and bypass of mating type locus control of sporulation.

    abstract::Sporulation in Saccharomyces cerevisiae normally occurs only in MATa/MAT alpha diploids. We show that mutations in RME1 bypassed the requirements for both a and alpha mating type information in sporulation and therefore allowed MATa/MATa and MAT alpha/MAT alpha diploids to sporulate. RME1 was located on chromosome VII...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Rine J,Sprague GF Jr,Herskowitz I

    更新日期:1981-10-01 00:00:00

  • Mutations affecting assembly and stability of tubulin: evidence for a nonessential beta-tubulin in CHO cells.

    abstract::Eight strains of Chinese hamster ovary (CHO) cells having an assembly-defective beta-tubulin were found among revertants of strain Cmd 4, a mutant with a conditional lethal mutation in a beta-tubulin gene (F. Cabral, M. E. Sobel, and M. M. Gottesman, Cell 20:29-36, 1980). The altered beta-tubulins in these strains hav...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Boggs B,Cabral F

    更新日期:1987-08-01 00:00:00

  • Overproduction of Rb protein after the G1/S boundary causes G2 arrest.

    abstract::The Rb protein is known to exert its activity at decision points in the G1 phase of the cell cycle. To investigate whether it may also play some role(s) at later points in the cell cycle, we used a system of rapid inducible gene amplification to conditionally overexpress Rb protein during G2 phase. A cell line express...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Karantza V,Maroo A,Fay D,Sedivy JM

    更新日期:1993-11-01 00:00:00

  • Deletion analysis identifies a region, upstream of the ADH2 gene of Saccharomyces cerevisiae, which is required for ADR1-mediated derepression.

    abstract::Deletion analysis was used to identify sequences upstream of the ADH2 gene of Saccharomyces cerevisiae that are required for its regulation. 5' and 3' internal deletions of the ADH2 control region were created in vitro, and the fragments were ligated adjacent to the ADH1 promoter and structural gene. Hybrid genes with...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Beier DR,Sledziewski A,Young ET

    更新日期:1985-07-01 00:00:00

  • Transient JMJD2B-mediated reduction of H3K9me3 levels improves reprogramming of embryonic stem cells into cloned embryos.

    abstract::Correct reprogramming of epigenetic marks in the donor nuclei is crucial for successful cloning by nuclear transfer. Specific epigenetic modifications, such as repressive histone lysine methylation marks, are known to be very stable and difficult to reprogram. The discovery of histone lysine demethylases has opened up...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Antony J,Oback F,Chamley LW,Oback B,Laible G

    更新日期:2013-03-01 00:00:00

  • Targeted disruption of the idol gene alters cellular regulation of the low-density lipoprotein receptor by sterols and liver x receptor agonists.

    abstract::Previously, we identified the E3 ubiquitin ligase Idol (inducible degrader of the low-density lipoprotein [LDL] receptor [LDLR]) as a posttranscriptional regulator of the LDLR pathway. Idol stimulates LDLR degradation through ubiquitination of its C-terminal domain, thereby limiting cholesterol uptake. Here we report ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Scotti E,Hong C,Yoshinaga Y,Tu Y,Hu Y,Zelcer N,Boyadjian R,de Jong PJ,Young SG,Fong LG,Tontonoz P

    更新日期:2011-05-01 00:00:00

  • Alternative processing of RNA transcribed from NMYC.

    abstract::NMYC is a gene whose amplification and overexpression have been implicated in the generation of certain human malignancies. Little is known of how the expression of NMYC is normally controlled. We have therefore characterized transcription from the gene and the structure and stability of the resulting mRNAs. Transcrip...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Stanton LW,Bishop JM

    更新日期:1987-12-01 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


    authors: Ford LP,Bagga PS,Wilusz J

    更新日期:1997-01-01 00:00:00

  • Alternative splicing of a human alpha-tropomyosin muscle-specific exon: identification of determining sequences.

    abstract::The human alpha-tropomyosin gene hTMnm has two mutually exclusive versions of exon 5 (NM and SK), one of which is expressed specifically in skeletal muscle (exon SK). A minigene construct expresses only the nonmuscle (NM) isoform when transfected into COS-1 cells and both forms when transfected into myoblasts. Twenty-...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Graham IR,Hamshere M,Eperon IC

    更新日期:1992-09-01 00:00:00

  • Isolation and transcriptional characterization of three genes which function at start, the controlling event of the Saccharomyces cerevisiae cell division cycle: CDC36, CDC37, and CDC39.

    abstract::The genes CDC36, CDC37, and CDC39, thought to function in the cell division control process in Saccharomyces cerevisiae, were isolated from a recombinant plasmid library prepared by partial digestion of S. cerevisiae genomic DNA with Sau3A and insertion into the S. cerevisiae-Escherichia coli shuttle vector YRp7. In e...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Breter HJ,Ferguson J,Peterson TA,Reed SI

    更新日期:1983-05-01 00:00:00

  • E2a/Pbx1 induces the rapid proliferation of stem cell factor-dependent murine pro-T cells that cause acute T-lymphoid or myeloid leukemias in mice.

    abstract::Oncoprotein E2a/Pbx1 is produced by the t(1;19) chromosomal translocation of human pre-B acute lymphoblastic leukemia. E2a/Pbx1 blocks differentiation of primary myeloid progenitors but, paradoxically, induces apoptosis in established pre-B-cell lines, and no transforming function of E2a/Pbx1 has been reported in cult...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Sykes DB,Kamps MP

    更新日期:2004-02-01 00:00:00

  • Phosphorylation of Par-4 by protein kinase A is critical for apoptosis.

    abstract::Despite distinct dissimilarities, diverse cancers express several common protumorigenic traits. We present here evidence that the proapoptotic protein Par-4 utilizes one such common tumorigenic trait to become selectively activated and induce apoptosis in cancer cells. Elevated protein kinase A (PKA) activity noted in...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Gurumurthy S,Goswami A,Vasudevan KM,Rangnekar VM

    更新日期:2005-02-01 00:00:00

  • A ubiquitin mutant with specific defects in DNA repair and multiubiquitination.

    abstract::The degradation of many proteins involves the sequential ligation of ubiquitin molecules to the substrate to form a multiubiquitin chain linked through Lys-48 of ubiquitin. To test for the existence of alternate forms of multiubiquitin chains, we examined the effects of individually substituting each of six other Lys ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Spence J,Sadis S,Haas AL,Finley D

    更新日期:1995-03-01 00:00:00

  • Hypoxia-inducible factors 1alpha and 2alpha regulate trophoblast differentiation.

    abstract::Placental development initially occurs in a low-oxygen (O2) or hypoxic environment. In this report we show that two hypoxia-inducible factors (HIFs), HIF1alpha and HIF2alpha, are essential for determining murine placental cell fates. HIF is a heterodimer composed of HIFalpha and HIFbeta (ARNT) subunits. Placentas from...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Cowden Dahl KD,Fryer BH,Mack FA,Compernolle V,Maltepe E,Adelman DM,Carmeliet P,Simon MC

    更新日期:2005-12-01 00:00:00

  • Immunosuppression by N-methyl-D-aspartate receptor antagonists is mediated through inhibition of Kv1.3 and KCa3.1 channels in T cells.

    abstract::N-methyl-D-aspartate receptors (NMDARs) are ligand-gated ion channels that play an important role in neuronal development, plasticity, and excitotoxicity. NMDAR antagonists are neuroprotective in animal models of neuronal diseases, and the NMDAR open-channel blocker memantine is used to treat Alzheimer's disease. In v...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Kahlfuß S,Simma N,Mankiewicz J,Bose T,Lowinus T,Klein-Hessling S,Sprengel R,Schraven B,Heine M,Bommhardt U

    更新日期:2014-03-01 00:00:00

  • The host gene for intronic U17 small nucleolar RNAs in mammals has no protein-coding potential and is a member of the 5'-terminal oligopyrimidine gene family.

    abstract::Intron-encoded U17a and U17b RNAs are members of the H/ACA-box class of small nucleolar RNAs (snoRNAs) participating in rRNA processing and modification. We have investigated the organization and expression of the U17 locus in human cells and found that intronic U17a and U17b sequences are transcribed as part of the t...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Pelczar P,Filipowicz W

    更新日期:1998-08-01 00:00:00

  • Essential role for mitochondrial thioredoxin reductase in hematopoiesis, heart development, and heart function.

    abstract::Oxygen radicals regulate many physiological processes, such as signaling, proliferation, and apoptosis, and thus play a pivotal role in pathophysiology and disease development. There are at least two thioredoxin reductase/thioredoxin/peroxiredoxin systems participating in the cellular defense against oxygen radicals. ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Conrad M,Jakupoglu C,Moreno SG,Lippl S,Banjac A,Schneider M,Beck H,Hatzopoulos AK,Just U,Sinowatz F,Schmahl W,Chien KR,Wurst W,Bornkamm GW,Brielmeier M

    更新日期:2004-11-01 00:00:00

  • The aryl hydrocarbon receptor mediates degradation of estrogen receptor alpha through activation of proteasomes.

    abstract::2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and other aryl hydrocarbon receptor (AhR) ligands suppress 17beta-estradiol (E)-induced responses in the rodent uterus and mammary tumors and in human breast cancer cells. Treatment of ZR-75, T47D, and MCF-7 human breast cancer cells with TCDD induces proteasome-dependent deg...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Wormke M,Stoner M,Saville B,Walker K,Abdelrahim M,Burghardt R,Safe S

    更新日期:2003-03-01 00:00:00

  • Coordination of RNA Polymerase II Pausing and 3' End Processing Factor Recruitment with Alternative Polyadenylation.

    abstract::Most mammalian genes produce transcripts whose 3' ends are processed at multiple alternative positions by cleavage/polyadenylation (CPA). Poly(A) site cleavage frequently occurs cotranscriptionally and is facilitated by CPA factor binding to the RNA polymerase II (Pol II) C-terminal domain (CTD) phosphorylated on Ser2...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Fusby B,Kim S,Erickson B,Kim H,Peterson ML,Bentley DL

    更新日期:2015-11-02 00:00:00

  • Development of autonomously replicating plasmids for Candida albicans.

    abstract::A pool of Candida albicans RsaI fragments cloned onto a vector containing pBR322 sequences and the Candida ADE2 gene was used to transform a Candida ade2 mutant to adenine protrophy. A potential autonomously replicating sequence (ARS) in Candida DNA was identified by two criteria: instability of the selectable marker ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Kurtz MB,Cortelyou MW,Miller SM,Lai M,Kirsch DR

    更新日期:1987-01-01 00:00:00

  • Specific acetylation of chromosomal protein HMG-17 by PCAF alters its interaction with nucleosomes.

    abstract::Nonhistone chromosomal proteins HMG-14 and HMG-17 are closely related nucleosomal binding proteins that unfold the higher-order chromatin structure, thereby enhancing the transcription and replication potential of chromatin. Here we report that PCAF, a transcription coactivator with intrinsic histone acetyltransferase...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Herrera JE,Sakaguchi K,Bergel M,Trieschmann L,Nakatani Y,Bustin M

    更新日期:1999-05-01 00:00:00

  • A 36-amino-acid region of CIITA is an effective inhibitor of CBP: novel mechanism of gamma interferon-mediated suppression of collagen alpha(2)(I) and other promoters.

    abstract::The class II transactivator (CIITA) is induced by gamma interferon (IFN-gamma) and activates major histocompatibility complex class II; however, this report shows it suppresses other genes. An N-terminal 36 amino acids of CIITA mediates suppression of the collagen alpha(2)(I) promoter via binding to CREB-binding prote...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Zhu XS,Ting JP

    更新日期:2001-10-01 00:00:00

  • Nucleocytoplasmic trafficking of the Syk protein tyrosine kinase.

    abstract::The protein tyrosine kinase Syk couples the B-cell receptor (BCR) for antigen to multiple intracellular signaling pathways and also modulates cellular responses to inducers of oxidative stress in a receptor-independent fashion. In B cells, Syk is found in both the nuclear and cytoplasmic compartments but contains no r...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Zhou F,Hu J,Ma H,Harrison ML,Geahlen RL

    更新日期:2006-05-01 00:00:00