Abstract:
:Rad53 of Saccharomyces cerevisiae is a checkpoint kinase whose structure and function are conserved among eukaryotes. When a cell detects damaged DNA, Rad53 activity is dramatically increased, which ultimately leads to changes in DNA replication, repair, and cell division. Despite its central role in checkpoint signaling, little is known about Rad53 substrates or substrate specificity. A number of proteins are implicated as Rad53 substrates; however, the evidence remains indirect. Previously, we have provided evidence that Swi6, a subunit of the Swi4/Swi6 late-G(1)-specific transcriptional activator, is a substrate of Rad53 in the G(1)/S DNA damage checkpoint. In the present study we identify Rad53 phosphorylation sites in Swi6 in vitro and demonstrate that at least one of them is targeted by Rad53 in vivo. Mutations in these phosphorylation sites in Swi6 shorten but do not eliminate the Rad53-dependent delay of the G(1)-to-S transition after DNA damage. We derive a consensus for Rad53 site preference at positions -2 and +2 (-2/+2) and identify its potential substrates in the yeast proteome. Finally, we present evidence that one of these candidates, the cohesin complex subunit Scc1 undergoes DNA damage-dependent phosphorylation, which is in part dependent on Rad53.
journal_name
Mol Cell Bioljournal_title
Molecular and cellular biologyauthors
Sidorova JM,Breeden LLdoi
10.1128/mcb.23.10.3405-3416.2003subject
Has Abstractpub_date
2003-05-01 00:00:00pages
3405-16issue
10eissn
0270-7306issn
1098-5549journal_volume
23pub_type
杂志文章abstract::We have previously identified poly(A)-binding protein 1 (PABP1) as a ligand for paxillin and shown that the paxillin-PABP1 complex undergoes nucleocytoplasmic shuttling. By targeting the paxillin-binding subdomain sequences in PABP1, we have generated mutants of PABP1 that do not bind to cellular paxillin. Here we rep...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.25.9.3763-3773.2005
更新日期:2005-05-01 00:00:00
abstract::In the budding yeast Saccharomyces cerevisiae, Cdc37 is required for the productive formation of Cdc28-cyclin complexes. The cdc37-1 mutant arrests at Start with low levels of Cdc28 protein, which is predominantly unphosphorylated at Thr169, fails to bind cyclin, and has little protein kinase activity. We show here th...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.20.3.749-754.2000
更新日期:2000-02-01 00:00:00
abstract::Chemical carcinogenesis in mouse skin has been useful in delineating the molecular events that underlie squamous cell carcinoma progression. A late event in this progression, the epithelial-to-mesenchymal transition (EMT), is characterized by the loss of epithelial markers and the presence of mesenchymal markers. One ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.21.16.5478-5487.2001
更新日期:2001-08-01 00:00:00
abstract::The pancreatic-islet-enriched transcription factors MafA and MafB have unique expression patterns in β cells in rodents. MafA is specifically expressed in β cells and is a key regulatory factor for maintaining adult β-cell function, whereas MafB plays an essential role in β-cell development during embryogenesis, and i...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00080-19
更新日期:2019-08-12 00:00:00
abstract::TRAF2 is an adaptor protein that regulates the activation of the c-Jun N-terminal kinase (JNK) and IkappaB kinase (IKK) signaling cascades in response to tumor necrosis factor alpha (TNF-alpha) stimulation. Although the downstream events in TNF-alpha signaling are better understood, the membrane-proximal events are st...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00699-08
更新日期:2009-01-01 00:00:00
abstract::The ubiquitin-proteasome pathway (UPP) is involved in regulation of multiple cellular processes. Hypoxia-inducible factor 1 alpha (HIF-1 alpha) is a prototypic target of the UPP and, as such, is stabilized under conditions of proteasomal inhibition. Using carbonic anhydrase IX (CAIX) and vascular endothelial growth fa...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00552-06
更新日期:2006-08-01 00:00:00
abstract::Interferon induces the synthesis of an enzyme which synthesizes 2',5'-oligoadenylate [2',5'-oligo(A)] when activated by double-stranded RNA. The 2',5'-oligo(A) in turn activates an endonuclease (RNase L). Concentrations of 2',5'-oligo(A) sufficient to activate RNase L are formed in interferon-treated HeLa cells infect...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.3.1.64
更新日期:1983-01-01 00:00:00
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
更新日期:1993-01-01 00:00:00
abstract::We describe a genetic transformation system which should prove useful for investigating tropomyosin assembly and function. Muscle abnormalities associated with a defective tropomyosin allele were corrected by integrating the wild-type gene into germ line chromosomes. The transformation protocol permits application of ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.7.8.2977
更新日期:1987-08-01 00:00:00
abstract::Glutamine is the preferred source of nitrogen of Neurospora crassa. In its presence and that of the gene product of MS5 (nmr-1), the fungus represses the assimilation of less preferred forms of nitrogen, such as nitrate. In the absence of glutamine and the presence of the product of gene nit-2, less preferred forms of...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.9.9.4113
更新日期:1989-09-01 00:00:00
abstract::The erbB-2 gene product, gp185erbB-2, unlike the structurally related epidermal growth factor (EGF) receptor (EGFR), exhibits constitutive kinase and transforming activity. We used a chimeric EGFR/erbB-2 expression vector to compare the mitogenic signaling pathway of the erbB-2 kinase with that of the EGFR, at similar...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.11.4.2040
更新日期:1991-04-01 00:00:00
abstract::The short form (S1b) of the prolactin receptor (PRLR) silences prolactin-induced activation of gene transcription by the PRLR long form (LF). The functional and structural contributions of two intramolecular disulfide (S-S) bonds within the extracellular subdomain 1 (D1) of S1b to its inhibitory function on the LF wer...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.01716-08
更新日期:2009-05-01 00:00:00
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 deacety...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.23.5.1602-1613.2003
更新日期:2003-03-01 00:00:00
abstract::We isolated a Drosophila fickleP (ficP) mutant with a shortened copulatory duration and reduced adult-stage life span. The reduced copulatory duration is ascribable to incomplete fusion of the left and right halves of the apodeme that holds the penis during copulation. ficP is an intronic mutation occurring in the Btk...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.19.6.4405
更新日期:1999-06-01 00:00:00
abstract::Simultaneous resistance to an array of drugs with different cytotoxic activities is a property of Saccharomyces cerevisiae, in which the protein Pdr3p has recently been shown to play a role as a transcriptional regulator. We provide evidence that the yeast PDR3 gene, which encodes a zinc finger transcription factor im...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.15.8.4043
更新日期:1995-08-01 00:00:00
abstract::Mutations in polycystin 2 (PC2), a Ca(2+)-permeable cation channel, cause autosomal dominant polycystic kidney disease. Whether PC2 functions in the endoplasmic reticulum (ER) or in the plasma membrane has been controversial. Here we generated and characterized a polyclonal antibody against PC2, determined the subcell...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.23.7.2600-2607.2003
更新日期:2003-04-01 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::We have determined the effects of a number of mutations in the small-t antigen mRNA intron on the alternative splicing pattern of the simian virus 40 early transcript. Expansion of the distance separating the small-t pre-mRNA lariat branch point and the shared large T-small t 3' splice site from 18 to 29 nucleotides (...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.8.9.3582
更新日期:1988-09-01 00:00:00
abstract::Complete replication of the genome is an essential prerequisite for normal cell division, but a variety of factors can block the replisome, triggering replication stress and potentially causing mutation or cell death. The cellular response to replication stress involves recruitment of proteins to stabilize the replica...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00472-17
更新日期:2018-03-29 00:00:00
abstract::Gamma interferon activation factor (GAF) rapidly induces transcriptional activation of gamma interferon (IFN-gamma)-responsive genes. Conversion of the GAF from a latent cytoplasmic to an activated, DNA-binding form is an immediate step in the cellular response to IFN-gamma. The amount of IFN-gamma-activated GAF, meas...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.13.6.3245
更新日期:1993-06-01 00:00:00
abstract::The Saccharomyces cerevisiae mitotic exit network (MEN) is a conserved set of genes that mediate the transition from mitosis to G(1) by regulating mitotic cyclin degradation and the inactivation of cyclin-dependent kinase (CDK). Here, we demonstrate that, in addition to mitotic exit, S. cerevisiae MEN gene MOB1 is req...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.21.20.6972-6983.2001
更新日期:2001-10-01 00:00:00
abstract::An unusual glucocorticoid-responsive element (called GRE A) was found to mediate the induction of the cytosolic aspartate aminotransferase gene by glucocorticoids and was bound by the glucocorticoid receptor in a DNase I footprinting assay. GRE A consists of two overlapping GREs, each comprising a conserved half-site ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.14.12.8007
更新日期:1994-12-01 00:00:00
abstract::Fractalkine (CX(3)CL1) is the first described chemokine that can exist either as a soluble protein or as a membrane-bound molecule. Both forms of fractalkine can mediate adhesion of cells expressing its receptor, CX(3)CR1. This activity, together with its expression on endothelial cells, suggests that fractalkine migh...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.21.9.3159-3165.2001
更新日期:2001-05-01 00:00:00
abstract::TRPV5 and TRPV6 are the most Ca2+-selective members of the transient receptor potential (TRP) family of cation channels and play a pivotal role in the maintenance of Ca2+ balance in the body. However, little is known about the mechanisms controlling the plasma membrane abundance of these channels to regulate epithelia...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.26.1.303-312.2006
更新日期:2006-01-01 00:00:00
abstract::The mammalian double-stranded RNA-activated protein kinase PKR is a component of the cellular antiviral defense mechanism and phosphorylates Ser-51 on the alpha subunit of the translation factor eIF2 to inhibit protein synthesis. To identify the molecular determinants that specify substrate recognition by PKR, we perf...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.17.7.4146
更新日期:1997-07-01 00:00:00
abstract::The chromatin structure of TDH3, one of three genes encoding glyceraldehyde phosphate dehydrogenases in Saccharomyces cerevisiae, was analyzed by nuclease digestion. A large hypersensitive region was found at the TDH3 promoter extending from the RNA initiation site at position -40 to position -560. This hypersensitive...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.8.12.5513
更新日期:1988-12-01 00:00:00
abstract::We have isolated a full-length mouse cDNA encoding a lysine-rich protein of 1,131 amino acids with a calculated molecular mass of 126 kDa. The protein binds in a sequence-unspecific manner to DNA, is localized exclusively in the nucleus, and contains a putative ATP binding site and a stretch of 80 amino acids with hom...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.14.3.1626
更新日期:1994-03-01 00:00:00
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
更新日期:2010-02-01 00:00:00
abstract::Double-strand breaks (DSBs) stimulate chromosomal and extrachromosomal recombination and gene targeting. Transcription also stimulates spontaneous recombination by an unknown mechanism. We used Saccharomyces cerevisiae I-SceI to stimulate recombination between neo direct repeats in Chinese hamster ovary (CHO) cell chr...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.17.11.6386
更新日期:1997-11-01 00:00:00
abstract::Chromatin is regulated by cross talk among different histone modifications, which can occur between residues within the same tail or different tails in the nucleosome. The latter is referred to as trans-tail regulation, and the best-characterized example of this is the dependence of H3 methylation on H2B ubiquitylatio...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00324-10
更新日期:2010-07-01 00:00:00