Abstract:
:mof6-1 was originally isolated as a recessive mutation in Saccharomyces cerevisiae which promoted increased efficiencies of programmed -1 ribosomal frameshifting and rendered cells unable to maintain the killer virus. Here, we demonstrate that mof6-1 is a unique allele of the histone deacetylase RPD3, that the deacetylase function of Rpd3p is required for controlling wild-type levels of frameshifting and virus maintenance, and that the closest human homolog can fully complement these defects. Loss of the Rpd3p-associated histone deacetylase function, either by mutants of rpd3 or loss of the associated gene product Sin3p or Sap30p, results in a delay in rRNA processing rather than in an rRNA transcriptional defect. This results in production of ribosomes having lower affinities for aminoacyl-tRNA and diminished peptidyltransferase activities. We hypothesize that decreased rates of peptidyl transfer allow ribosomes with both A and P sites occupied by tRNAs to pause for longer periods of time at -1 frameshift signals, promoting increased programmed -1 ribosomal frameshifting efficiencies and subsequent loss of the killer virus. The frameshifting defect is accentuated when the demand for ribosomes is highest, suggesting that rRNA posttranscriptional modification is the bottleneck in ribosome biogenesis.
journal_name
Mol Cell Bioljournal_title
Molecular and cellular biologyauthors
Meskauskas A,Baxter JL,Carr EA,Yasenchak J,Gallagher JE,Baserga SJ,Dinman JDdoi
10.1128/mcb.23.5.1602-1613.2003subject
Has Abstractpub_date
2003-03-01 00:00:00pages
1602-13issue
5eissn
0270-7306issn
1098-5549journal_volume
23pub_type
杂志文章abstract::2-Aminopurine (2-AP) inhibits specific kinases that phosphorylate the alpha subunit of eukaryotic translation initiation factor 2. One of these, PKR, is also involved in signal transduction. We show here that 2-AP selectively inhibits expression of tumor necrosis factor alpha (TNF-alpha) mRNA in primary human lymphoid...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.16.6.2814
更新日期:1996-06-01 00:00:00
abstract::To understand the mechanism of Axl signaling, we have initiated studies to delineate downstream components in interleukin-3-dependent 32D cells by using a chimeric receptor containing the recombinant epidermal growth factor (EGF) receptor extracellular and transmembrane domains and the Axl kinase domain (EAK [for EGF ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.16.1.135
更新日期:1996-01-01 00:00:00
abstract::Sphingolipid metabolism is implicated to play an important role in apoptosis. Here we show that dihydrosphingosine (DHS) and phytosphingosine (PHS), two major sphingoid bases of fungi, have potent fungicidal activity with remarkably high structural and stereochemical specificity against Aspergillus nidulans. In fact, ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.23.1.163-177.2003
更新日期:2003-01-01 00:00:00
abstract::We have combined in vitro DNA replication reactions and immunological techniques to analyze biochemical interactions between simian virus (SV40) large T antigen and components of the cellular replication apparatus. First, in vitro SV40 DNA replication was characterized with specific origin mutants. Next, monoclonal an...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.6.11.4077
更新日期:1986-11-01 00:00:00
abstract::GPR103 is a G-protein-coupled receptor with reported expression in brain, heart, kidney, adrenal gland, retina, and testis. It encodes a 455-amino-acid protein homologous to neuropeptide FF2, neuropeptide Y2, and galanin GalR1 receptors. Its natural ligand was recently identified as 26RFa, a novel human RF-amide-relat...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.26.2.709-717.2006
更新日期:2006-01-01 00:00:00
abstract::We have identified a gene that encodes the polypeptide cytochrome b in the avian malarial parasite Plasmodium gallinaceum. The gene containing the open reading frame was found to be located on a 6.2-kilobase multimeric extrachromosomal element. The amino acid translation from this gene demonstrated significant similar...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.9.9.3614
更新日期:1989-09-01 00:00:00
abstract::Ribosomal protein L5 binds specifically to 5S rRNA to form a complex that is a precursor to 60S subunit assembly in vivo. Analyses in yeast cells, mammalian cells, and Xenopus embryos have shown that the accumulation of L5 is not coordinated with the expression of other ribosomal proteins. In this study, the primary s...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.9.12.5281
更新日期:1989-12-01 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::Ubiquitously expressed transcription factors play an integral role in establishing and regulating patterns of gene transcription. Common factor 1 (CF1) is a ubiquitously expressed DNA-binding protein previously identified in our laboratory. We show here that CF1 recognizes sites in several diverse transcription elemen...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.11.3.1765
更新日期:1991-03-01 00:00:00
abstract::A transcriptional initiator (Inr) for mammalian RNA polymerase II can be defined as a DNA sequence element that overlaps a transcription start site and is sufficient for (i) determining the start site location in a promoter that lacks a TATA box and (ii) enhancing the strength of a promoter that contains a TATA box. W...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.14.1.116
更新日期:1994-01-01 00:00:00
abstract::Janus kinases are essential for signal transduction by a variety of cytokine receptors and when inappropriately activated can cause hematopoietic disorders and oncogenesis. Consequently, it can be predicted that the interaction of the kinases with receptors and the events required for activation are highly controlled....
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.01447-07
更新日期:2008-03-01 00:00:00
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
更新日期:2001-03-01 00:00:00
abstract::We isolated and characterized LP1.2, a mouse myeloma mutant with a deletion of at least 4 kilobases (kb) immediately 3' of the alpha gene and introduction of at least 5 kb of novel (nonimmunoglobulin) sequence in its place. A 6.2-kb genomic EcoRI fragment from the mutated allele was cloned, and a subfragment was seque...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.6.6.1903
更新日期:1986-06-01 00:00:00
abstract::Eukaryotic viruses have devised numerous strategies to downregulate activity of the interferon-induced, double-stranded (dsRNA)-activated protein kinase (referred to as p68 on the basis of its Mr of 68,000 in human cells). Viruses must exert this control to avoid extensive phosphorylation of the alpha subunit of eukar...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.11.11.5497
更新日期:1991-11-01 00:00:00
abstract::Alkylpurine-DNA-N-glycosylase (APNG) null mice have been generated by homologous recombination in embryonic stem cells. The null status of the animals was confirmed at the mRNA level by reverse transcription-PCR and by the inability of cell extracts of tissues from the knockout (ko) animals to release 3-methyladenine ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.18.10.5828
更新日期:1998-10-01 00:00:00
abstract::We analyzed the transcriptional properties of a repetitive sequence element, BmX, that belongs to a large gene family (approximately 2 x 10(4) copies) in the genome of the Bombyx mori silkworm. We discovered BmX elements because of their ability to direct transcription by polymerase III in vitro and used them to test ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.8.2.624
更新日期:1988-02-01 00:00:00
abstract::Transfection of a hamster cell mutant with human DNA corrected both the low-density lipoprotein receptor-deficient phenotype and the multiple glycosylation defects of the cells. Independently transfected colonies contained a small set of common human DNA fragments. These fragments may correspond to the human analog of...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.6.7.2734
更新日期:1986-07-01 00:00:00
abstract::Previous studies have identified novel modifications in the core fold domain of histone H2B, but relatively little is known about the function of these putative histone modification sites. We have mutated core modifiable residues that are conserved in Saccharomyces cerevisiae histone H2B and characterized the effects ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00290-10
更新日期:2010-07-01 00:00:00
abstract::Transcriptional activators interact with multisubunit coactivators that modify chromatin structure or recruit the general transcriptional machinery to their target genes. Budding yeast cells respond to amino acid starvation by inducing an activator of amino acid biosynthetic genes, Gcn4p. We conducted a comprehensive ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.23.8.2800-2820.2003
更新日期:2003-04-01 00:00:00
abstract::Nuclear expression and consequent biological action of the eukaryotic NF-kappa B transcription factor complex are tightly regulated through its cytoplasmic retention by an ankyrin-rich inhibitory protein termed I kappa B alpha. I kappa B alpha specifically binds to and masks the nuclear localization signal of the RelA...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.16.3.1058
更新日期:1996-03-01 00:00:00
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
更新日期:1989-05-01 00:00:00
abstract::c-Myc promotes apoptosis by destabilizing mitochondrial integrity, leading to the release of proapoptotic effectors including holocytochrome c. Candidate mediators of c-Myc in this process are the proapoptotic members of the Bcl-2 family. We show here that fibroblasts lacking Bak remain susceptible to c-Myc-induced ap...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.22.17.6158-6169.2002
更新日期:2002-09-01 00:00:00
abstract::To investigate the mechanisms by which transcription factors invade nucleosomal DNA and replace histones at control elements, we have examined the response of the histone octamer to transcription factor binding in the presence of histone-binding proteins (i.e., nucleosome assembly factors). We found that yeast nucleos...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.15.11.6178
更新日期:1995-11-01 00:00:00
abstract::Ret/ptc2 is a constitutively active, oncogenic form of the c-Ret receptor tyrosine kinase. Like the other papillary thyroid carcinoma forms of Ret, Ret/ptc2 is activated through fusion of the Ret tyrosine kinase domain to the dimerization domain of another protein. Investigation of requirements for Ret/ptc2 mitogenic ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.18.4.2298
更新日期:1998-04-01 00:00:00
abstract::Using competition mobility shift, methylation interference, and proteolytic clipping DNA binding assays, we demonstrate that the protein binding the major histocompatibility complex A beta CCAAT box is indistinguishable from the protein previously named NF-Y, which binds the major histocompatibility complex E alpha CC...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.11.1.578
更新日期:1991-01-01 00:00:00
abstract::Kss1 and Fus3 are mitogen-activated protein kinases (MAPKs or ERKs), and Ste7 is their activating MAPK/ERK kinase (MEK), in the pheromone response pathway of Saccharomyces cerevisiae. To investigate the potential role of specific interactions between these enzymes during signaling, their ability to associate with each...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.16.7.3637
更新日期:1996-07-01 00:00:00
abstract::The rad18 gene of Schizosaccharomyces pombe is an essential gene that is involved in several different DNA repair processes. Rad18 (Smc6) is a member of the structural maintenance of chromosomes (SMC) family and, together with its SMC partner Spr18 (Smc5), forms the core of a high-molecular-weight complex. We show her...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.25.1.172-184.2005
更新日期:2005-01-01 00:00:00
abstract::We describe an interaction between homeodomain-interacting protein kinase 1 (HIPK1) and Daxx, two transcriptional regulators important in transducing growth-regulatory signals. We demonstrate that HIPK1 is ubiquitously expressed in mice and humans and localizes predominantly to the nucleus. Daxx normally resides withi...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.23.3.950-960.2003
更新日期:2003-02-01 00:00:00
abstract::Various stresses activate the c-Jun N-terminal kinase (JNK), which is involved in the regulation of many aspects of cellular physiology, including apoptosis. Here we demonstrate that in contrast to UV irradiation, heat shock causes little or no stimulation of the JNK-activating kinase SEK1, while knocking out the SEK1...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.19.4.2547
更新日期:1999-04-01 00:00:00
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
更新日期:1996-08-01 00:00:00