Abstract:
:CCAAT/enhancer binding protein beta (C/EBPbeta) is a widely expressed transcription factor whose activity is regulated by oncogenic Ha-RasV12 signaling. C/EBPbeta is essential for the development of mouse skin tumors containing Ras mutations and can cooperate with RasV12 to transform NIH 3T3 cells. Here we have investigated Ras-induced phosphorylation of C/EBPbeta in fibroblasts and report a novel proline-directed phosphoacceptor site at Ser64 within the transactivation domain. Ser64 phosphorylation was induced by activated Ras and Raf but was not blocked by chemical inhibitors of MEK1/2, phosphatidylinositol 3-kinase, JNK, or p38 mitogen-activated protein kinases. Ser64 was efficiently phosphorylated in vitro by the cyclin-dependent kinases Cdk2 and Cdc2. Thr189, previously identified as an ERK1/2 phosphorylation site that regulates C/EBPbeta activity, was also a substrate for Cdk phosphorylation. Ser64 and Thr189 phosphorylation was low in serum-starved (G0) cells but was strongly increased in mid-G1 cells and in cells arrested in S or M phase. In addition, phosphorylation on both sites was blocked by treating cells with the Cdk inhibitor roscovitine. In contrast to wild-type C/EBPbeta, which enhances transformation of NIH 3T3 cells, mutants bearing alanine substitutions at Ser64 and/or Thr189 inhibited RasV12-induced focus formation. Our findings support a role for C/EBPbeta as a nuclear effector of Ras signaling and transformation, and they indicate that cell cycle-dependent phosphorylation of C/EBPbeta on Ser64 and Thr189 is required to promote Ras-induced transformation of NIH 3T3 cells.
journal_name
Mol Cell Bioljournal_title
Molecular and cellular biologyauthors
Shuman JD,Sebastian T,Kaldis P,Copeland TD,Zhu S,Smart RC,Johnson PFdoi
10.1128/MCB.24.17.7380-7391.2004subject
Has Abstractpub_date
2004-09-01 00:00:00pages
7380-91issue
17eissn
0270-7306issn
1098-5549pii
24/17/7380journal_volume
24pub_type
杂志文章abstract::Secretory proteins in eukaryotic cells are transported to the cell surface via the endoplasmic reticulum (ER) and the Golgi apparatus by membrane-bounded vesicles. We screened a collection of temperature-sensitive mutants of Saccharomyces cerevisiae for defects in ER-to-Golgi transport. Two of the genes identified in ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.18.12.7139
更新日期:1998-12-01 00:00:00
abstract::In Saccharomyces cerevisiae, the Wee1 family kinase Swe1p is normally stable during G(1) and S phases but is unstable during G(2) and M phases due to ubiquitination and subsequent degradation. However, perturbations of the actin cytoskeleton lead to a stabilization and accumulation of Swe1p. This response constitutes ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.19.10.6929
更新日期:1999-10-01 00:00:00
abstract::R-loops have been described in vivo at the immunoglobulin class switch sequences and at prokaryotic and mitochondrial origins of replication. However, the biochemical mechanism and determinants of R-loop formation are unclear. We find that R-loop formation is nearly eliminated when RNase T(1) is added during transcrip...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.01251-07
更新日期:2008-01-01 00:00:00
abstract::Human antigen R (ELAVL1; HuR) is perhaps the best-characterized RNA-binding protein. Through its overexpression in various tumor types, HuR promotes posttranscriptional regulation of target genes in multiple core signaling pathways associated with tumor progression. The role of HuR overexpression in pancreatic tumorig...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00427-17
更新日期:2018-01-16 00:00:00
abstract::The mouse myosin light-chain 1A (MLC1A) gene, expressed in the atria of the adult heart, is one of the first muscle genes to be activated when skeletal as well as cardiac muscles form in the embryo. It is also transcribed in skeletal muscle cell lines at the onset of differentiation. Transient transfection assays of m...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.15.8.4585
更新日期:1995-08-01 00:00:00
abstract::Human insulin-like growth factor II (IGF-II) mRNAs are subject to site-specific endonucleolytic cleavage in the 3' untranslated region, leading to an unstable 5' cleavage product containing the IGF-II coding region and a very stable 3' cleavage product of 1.8 kb. This endonucleolytic cleavage is most probably the firs...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.15.1.235
更新日期:1995-01-01 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::The active beta-globin genes in chicken erythrocytes, like all active genes, reside in large chromatin domains which are preferentially sensitive to digestion by DNase I. We have recently proposed that the special structure of chromatin in active domains is maintained by torsional stress in the DNA (Villeponteau et al...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.7.5.1917
更新日期:1987-05-01 00:00:00
abstract::FUD6, a nonphotosynthetic mutant of Chlamydomonas reinhardtii, was previously found to be deficient in the synthesis of subunit IV of the cytochrome b6/f complex, the chloroplast petD gene product (C. Lemaire, J. Girard-Bascou, F.-A. Wollman, and P. Bennoun, Biochim. Biophys. Acta 851:229-238, 1986). The lesion in FUD...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.14.9.6171
更新日期:1994-09-01 00:00:00
abstract::Mouse mammary tumor virus (MMTV) promoter-driven transcription is induced by glucocorticoid hormone via binding of the glucocorticoid receptor (GR). The MMTV promoter also harbors a binding site for nuclear factor 1 (NF1). NF1 and GR were expressed in Xenopus oocytes; this revealed GR-NF1 cooperativity both in terms o...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.24.7.3036-3047.2004
更新日期:2004-04-01 00:00:00
abstract::The Saccharomyces cerevisiae PGK (phosphoglycerate kinase) gene encodes one of the most abundant mRNA and protein species in the cell. To identify the promoter sequences required for the efficient expression of PGK, we undertook a detailed internal deletion analysis of the 5' noncoding region of the gene. Our analysis...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.6.12.4335
更新日期:1986-12-01 00:00:00
abstract::Expression of the Saccharomyces cerevisiae CYC1 gene produces mRNA with more than 20 different 5' ends. A derivative of the CYC1 gene (CYC1-157) was constructed with a deletion of a portion of the CYC1 5'-noncoding region, which includes the sites at which many of the CYC1 mRNAs 5' ends map. A 54-mer double-stranded o...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.5.12.3545
更新日期:1985-12-01 00:00:00
abstract::Cloned segments of the mouse glycerol-3-phosphate dehydrogenase (GPDH) gene, Gdc-1, were used to screen a human library. Human clones obtained spanned 25 kilobases of genomic DNA containing the human GPDH gene, GPD1. The 4 kb of sequence obtained from the 5'-flanking region and first exon of GPD1 was compared with the...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.10.10.5244
更新日期:1990-10-01 00:00:00
abstract::The expression of chromosomally integrated transgenes usually varies greatly among independent transfectants. This variability in transgene expression has led to the definition of locus control regions (LCRs) as elements which render expression consistent. Analyses of expression in single cells revealed that the expre...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.19.10.7031
更新日期:1999-10-01 00:00:00
abstract::We have constructed a recombinant pBR322 plasmid composed of a subgenomic transforming fragment of bovine papillomavirus DNA and the hepatitis B surface antigen gene from cloned hepatitis B virus DNA and used it for transfection of NIH 3T3 mouse fibroblasts. The transformed cells retain the plasmids in extrachromosoma...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.3.6.1032
更新日期:1983-06-01 00:00:00
abstract::Telomerase promotes telomere maintenance by copying a template within its integral RNA subunit to elongate chromosome ends with new telomeric repeats. Motifs have been defined within the telomerase RNA that contribute to mature RNA accumulation, holoenzyme catalytic activity, or enzyme recruitment to telomeres. Here, ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.01033-10
更新日期:2011-02-01 00:00:00
abstract::Interleukin-5 (IL-5) is produced by T lymphocytes and known to support B-cell growth and eosinophilic differentiation of the progenitor cells. Using ATL-16T cells which express IL-5 mRNA, we have identified a region within the human IL-5 gene promoter that regulates IL-5 gene transcription. This cis-acting sequence co...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.15.7.3830
更新日期:1995-07-01 00:00:00
abstract::Progesterone receptor (PR) and ErbB-2 bidirectional cross talk participates in breast cancer development. Here, we identified a new mechanism of the PR and ErbB-2 interaction involving the PR induction of ErbB-2 nuclear translocation and the assembly of a transcriptional complex in which ErbB-2 acts as a coactivator o...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00012-10
更新日期:2010-12-01 00:00:00
abstract::The B-lymphocyte- and macrophage-specific transcription factor PU.1 is a member of the ets family of proteins. To understand how PU.1 functions as a transcription factor, we initiated a series of experiments to define its activation domain. Using deletion analysis, we showed that the activation domain of PU.1 is locat...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.16.1.390
更新日期:1996-01-01 00:00:00
abstract::To interrogate endogenous p21(WAF1/CIP1) (p21) promoter activity under basal conditions and in response to various forms of stress, knock-in imaging reporter mice in which expression of firefly luciferase (FLuc) was placed under the control of the endogenous p21 promoter within the Cdkn1a gene locus were generated. Bi...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.05243-11
更新日期:2011-09-01 00:00:00
abstract::Giardia lamblia trophozoites demonstrate variable expression of a repertoire of cysteine-rich surface antigens in vitro and in vivo. The size of the repertoire has been estimated at 20 to 184, and specific variants can be detected after approximately 12 generations of in vitro growth for the WB isolate. In earlier stu...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.12.3.1194
更新日期:1992-03-01 00:00:00
abstract::The 3' noncoding region element (AUUUA)n specifically targets many short-lived mRNAs for degradation. Although the mechanism by which this sequence functions is not yet understood, a potential link between facilitated mRNA turnover and translation has been implied by the stabilization of cellular mRNAs in the presence...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.13.3.1971
更新日期:1993-03-01 00:00:00
abstract::G proteins are molecular switches that control a wide variety of physiological functions, including neurotransmission, transcriptional activation, cell migration, cell growth. and proliferation. The ability of GTPases to participate in signaling events is determined by the ratio of GTP-bound to GDP-bound forms in the ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.23.7.2476-2488.2003
更新日期:2003-04-01 00:00:00
abstract::Splicing of tRNA precursors in Saccharomyces cerevisiae extracts proceeds in two steps; excision of the intervening sequence and ligation of the tRNA halves. The ability to resolve these two steps and the distinct physical properties of the endonuclease and ligase suggested that the splicing steps may not be concerted...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.6.2.635
更新日期:1986-02-01 00:00:00
abstract::The ALCR protein is the transcriptional activator of the ethanol utilization pathway in the filamentous fungus Aspergillus nidulans. This activator belongs to a family of fungal proteins having a conserved DNA-binding domain containing six cysteines (C6 class) with some striking features. At variance with other motifs...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.12.5.1932
更新日期:1992-05-01 00:00:00
abstract::We have characterized a pathway for nuclear export of the glucocorticoid receptor (GR) in mammalian cells. This pathway involves the Ca2+ -binding protein calreticulin (CRT), which directly contacts the DNA binding domain (DBD) of GR and facilitates its delivery from the nucleus to the cytoplasm. In the present study,...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.22.17.6286-6297.2002
更新日期:2002-09-01 00:00:00
abstract::The gene encoding human hemojuvelin (HJV) is one of the genes that, when mutated, can cause juvenile hemochromatosis, an early-onset inherited disorder associated with iron overload. The 5' untranslated region of the human HJV mRNA has two upstream open reading frames (uORFs), with 28 and 19 codons formed by two upstr...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.01462-14
更新日期:2015-04-01 00:00:00
abstract::The carboxyl-terminal domain (CTD) of RNA polymerase II (Pol II) can be phosphorylated at serine 2 (Ser-2) and serine 5 (Ser-5) of the CTD heptad repeat YSPTSPS, and this phosphorylation is important in coupling transcription to RNA processing, including 5' capping, splicing, and polyadenylation. The mammalian endogen...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.23.6.1961-1967.2003
更新日期:2003-03-01 00:00:00
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
doi:10.1128/mcb.3.5.881
更新日期:1983-05-01 00:00:00
abstract::Sirtuins are a family of protein deacetylases, deacylases, and ADP-ribosyltransferases that regulate life span, control the onset of numerous age-associated diseases, and mediate metabolic homeostasis. We have uncovered a novel role for the mitochondrial sirtuin SIRT4 in the regulation of hepatic lipid metabolism duri...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00087-13
更新日期:2013-11-01 00:00:00