The Cloning and Analyses of Human Cellular Genes Homologous to Retroviral Onc Genes

1983 ◽  
pp. 479-492
Author(s):  
Flossie Wong-Staal ◽  
Eric Westin ◽  
Genoveffa Franchini ◽  
Edward Gelmann ◽  
Riccardo Dalla Favera ◽  
...  
Keyword(s):  
Cellular Genes

scholarly journals Molecular cloning of cellular genes encoding retinoblastoma-associated proteins: identification of a gene with properties of the transcription factor E2F.

1992 ◽  
Vol 12 (12) ◽  
pp. 5620-5631 ◽  
Author(s):  
B Shan ◽  
X Zhu ◽  
P L Chen ◽  
T Durfee ◽  
Y Yang ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Mammalian Cells ◽  
Leucine Zipper ◽  
T Antigen ◽  
Transactivation Domain ◽  
Recognition Sequence ◽  
Cellular Genes ◽  
Genes Encoding ◽  
Associated Proteins ◽  
Transcription Factor E2f

The retinoblastoma protein interacts with a number of cellular proteins to form complexes which are probably crucial for its normal physiological function. To identify these proteins, we isolated nine distinct clones by direct screening of cDNA expression libraries using purified RB protein as a probe. One of these clones, Ap12, is expressed predominantly at the G1-S boundary and in the S phase of the cell cycle. The nucleotide sequence of Ap12 has features characteristic of transcription factors. The C-terminal region binds to unphosphorylated RB in regions similar to those to which T antigen binds and contains a transactivation domain. A region containing a potential leucine zipper flanked by basic residues is able to bind an E2F recognition sequence specifically. Expression of Ap12 in mammalian cells significantly enhances E2F-dependent transcriptional activity. These results suggest that Ap12 encodes a protein with properties known to be characteristic of transcription factor E2F.

scholarly journals trans-dominant mutants of E1A provide genetic evidence that the zinc finger of the trans-activating domain binds a transcription factor.

1991 ◽  
Vol 11 (9) ◽  
pp. 4287-4296 ◽  
Author(s):  
L C Webster ◽  
R P Ricciardi
Keyword(s):  
Transcription Factor ◽  
Zinc Finger ◽  
Cellular Protein ◽  
Site Directed Mutagenesis ◽  
Cellular Transcription Factor ◽  
Dominant Phenotype ◽  
Cellular Genes ◽  
Critical Residue ◽  
The Individual ◽  
Cellular Transcription

The 289R E1A protein of adenovirus stimulates transcription of early viral and certain cellular genes. trans-Activation requires residues 140 to 188, which encompass a zinc finger. Several studies have indicated that trans-activation by E1A is mediated through cellular transcription factors. In particular, the ability of the trans-dominant E1A point mutant hr5 (Ser-185 to Asn) to inhibit wild-type E1A trans-activation was proposed to result from the sequestration of a cellular factor. Using site-directed mutagenesis, we individually replaced every residue within and flanking the trans-activating domain with a conservative amino acid, revealing 16 critical residues. Six of the individual substitutions lying in a contiguous stretch C terminal to the zinc finger (carboxyl region183-188) imparted a trans-dominant phenotype. trans-Dominance was even produced by deletion of the entire carboxyl region183-188. Conversely, an intact finger region147-177 was absolutely required for trans-dominance, since second-site substitution of every critical residue in this region abrogated the trans-dominant phenotype of the hr5 protein. These data indicate that the finger region147-177 bind a limiting cellular transcription factor and that the carboxyl region183-188 provides a separate and essential function. In addition, we show that four negatively charged residues within the trans-activating domain do not comprise a distinct acidic activating region. We present a model in which the trans-activating domain of E1A binds to two different cellular protein targets through the finger and carboxyl regions.

A cDNA for a human cyclic AMP response element-binding protein which is distinct from CREB and expressed preferentially in brain

1990 ◽  
Vol 10 (4) ◽  
pp. 1347-1357
Author(s):  
C J Kara ◽  
H C Liou ◽  
L B Ivashkiv ◽  
L H Glimcher
Keyword(s):  
Dna Binding ◽  
Cyclic Amp ◽  
Leucine Zipper ◽  
Binding Protein ◽  
Structural Similarity ◽  
Response Element ◽  
Cellular Genes ◽  
Viral Promoters ◽  
Element Binding Protein ◽  
Cyclic Amp Response Element

The cyclic AMP response element (CRE) is found in many cellular genes regulated by cyclic AMP, and similar elements are present in the early genes of adenovirus that are activated by E1A. The transcription factor CREB has previously been shown to bind this site, and cDNAs for CREB have recently been characterized. We report here the isolation of a cDNA encoding a human DNA-binding protein that also recognizes this motif in cellular and viral promoters. This protein, HB16, displays structural similarity to CREB and to c-Jun and c-Fos, which bind the related 12-O-tetradecanoylphorbol-13-acetate response element (TRE). HB16 contains a highly basic, putative DNA-binding domain and a leucine zipper structure thought to be involved in dimerization. Deletional analysis of HB16 demonstrated that the leucine zipper is required for its interaction with DNA. In addition, HB16 could form a complex with c-Jun but not with c-Fos. Despite its structural similarity to c-Jun and c-Fos and its interaction with c-Jun, HB16 had approximately a 10-fold-lower affinity for the TRE sequence than for the CRE sequence. Although HB16 and CREB both recognized the CRE motif, an extensive binding analysis of HB16 revealed differences in the fine specificity of binding of the two proteins. HB16 mRNA was found at various levels in many human tissues but was most abundant in brain, where its expression was widespread. The existence of more than one CRE-binding protein suggests that the CRE motif could serve multiple regulatory functions.

Rapid induction of polyadenylated H1 histone mRNAs in mouse erythroleukemia cells is regulated by c-myc

1989 ◽  
Vol 9 (6) ◽  
pp. 2332-2340
Author(s):  
G H Cheng ◽  
A I Skoultchi
Keyword(s):  
Terminal Differentiation ◽  
Histone Genes ◽  
H1 Histone ◽  
Rapid Induction ◽  
Histone Mrnas ◽  
Cellular Genes ◽  
Erythroleukemia Cells ◽  
Multistep Process ◽  
Murine Erythroleukemia ◽  
Mouse Erythroleukemia

Chemically induced differentiation of murine erythroleukemia cells is a multistep process involving a precommitment period in which exposure to inducer leads to cells that are irreversibly committed to terminal differentiation. Certain changes in the expression of cellular proto-oncogenes are an important feature of the precommitment phase. We have identified two H1 histone genes that are rapidly induced during this period. Unlike most histone genes, these two H1 genes encode polyadenylated mRNAs with long 3' untranslated regions. To investigate the relationship between induction of the H1 mRNAs and changes in proto-oncogene expression, we studied two independent series of mouse erythroleukemia cell lines that are inhibited from differentiating because of deregulated expression of transfected copies of c-myc or c-myb. The results showed that induction of the H1 mRNAs was negatively regulated by c-myc. The two H1 histone genes are among the first examples of specific cellular genes that are regulated by c-myc. The timing of their induction suggests that they may play an important role in achieving commitment to terminal differentiation.

Cellular oncogenes (c-erb-A and c-erb-B) located on different chicken chromosomes can be transduced into the same retroviral genome

1984 ◽  
Vol 4 (8) ◽  
pp. 1627-1630
Author(s):  
G Symonds ◽  
E Stubblefield ◽  
M Guyaux ◽  
J M Bishop
Keyword(s):  
Chicken Genome ◽  
Large Chromosome ◽  
Cellular Genes ◽  
Intermediate Size ◽  
Avian Erythroblastosis Virus ◽  
Cellular Oncogenes

Avian erythroblastosis virus has transduced two cellular genes, c-erb-A and c-erb-B. Using fractionated chicken chromosomes, we found that the two genes are located on different chromosomes in the chicken genome: c-erb-A is on a microchromosome, and c-erb-B is on a large chromosome. The locations of two other cellular oncogenes (c-fps and c-myb) were also determined: c-fps is on a microchromosome, and c-myb is on chromosome of an intermediate size. Our results suggest that avian erythroblastosis virus had transduced the two cellular genes independently, conforming to previous indications that cellular oncogenes are dispersed among multiple chromosomes in every species that has been examined.

scholarly journals Identification of Homeodomain Proteins, PBX1 and PREP1, Involved in the Transcription of Murine Leukemia Virus

2003 ◽  
Vol 23 (3) ◽  
pp. 831-841 ◽  
Author(s):  
Sheng-Hao Chao ◽  
John R. Walker ◽  
Sumit K. Chanda ◽  
Nathanael S. Gray ◽  
Jeremy S. Caldwell
Keyword(s):  
Murine Leukemia Virus ◽  
Kinase Inhibitors ◽  
Leukemia Virus ◽  
Moloney Murine Leukemia Virus ◽  
Viral Transcription ◽  
Long Terminal Repeats ◽  
Homeodomain Proteins ◽  
Cellular Genes ◽  
Simplex Virus ◽  
Murine Leukemia

ABSTRACT Cyclin-dependent kinase inhibitors (CDKIs) have been shown to block human immunodeficiency virus and herpes simplex virus. It is hypothesized that CDKIs block viral replication by inhibiting transcription of specific cellular genes. Here we find that three CDKIs, flavopiridol, purvalanol A, and methoxy-roscovitine, block Moloney murine leukemia virus (MLV) transcription events. Using gene expression microarray technology to examine the inhibitory effects of CDKIs, we observed a cellular gene, the pre-B-cell leukemia transcription factor 1 (Pbx1) gene, down-regulated by CDKI treatment. The PBX consensus element (PCE), TGATTGAC, is conserved in the long terminal repeats of several murine retroviruses, including Moloney MLV. Mutations in the PCE completely inhibited viral transcription whereas overexpression of PBX1 and a PBX1-associated protein, PREP1, enhanced viral transcription. The interaction between the PCE and PBX1-PREP1 proteins was confirmed by gel shift experiments. Blocking PBX1 protein synthesis resulted in a significant decrease in viral transcription. Collectively, our results represent the first work demonstrating that the homeodomain proteins PBX1 and PREP1 are cellular factors involved in Moloney MLV transcription regulation.

scholarly journals Inhibition of Host Protein Synthesis and Degradation of Cellular mRNAs During Infection by Influenza and Herpes Simplex Virus

1982 ◽  
Vol 2 (12) ◽  
pp. 1644-1648 ◽  
Author(s):  
S. C. Inglis
Keyword(s):  
Protein Synthesis ◽  
Blot Hybridization ◽  
Host Protein ◽  
Cell Protein ◽  
Cellular Genes ◽  
Cellular Mrnas ◽  
The Stability ◽  
Simplex Virus ◽  
Host Protein Synthesis ◽  
Synthesis And Degradation

Cloned DNA copies of two cellular genes were used to monitor, by blot hybridization, the stability of particular cell mRNAs after infection by influenza virus and herpesvirus. The results indicated that the inhibition of host cell protein synthesis that accompanied infection by each virus could be explained by a reduction in the amounts of cellular mRNAs in the cytoplasm, and they suggested that this decrease was due to virus-mediated mRNA degradation.

scholarly journals Human GATA-3 trans-activation, DNA-binding, and nuclear localization activities are organized into distinct structural domains.

1994 ◽  
Vol 14 (3) ◽  
pp. 2201-2212 ◽  
Author(s):  
Z Yang ◽  
L Gu ◽  
P H Romeo ◽  
D Bories ◽  
H Motohashi ◽  
...  
Keyword(s):  
Amino Acids ◽  
Dna Binding ◽  
Zinc Finger ◽  
Nuclear Localization ◽  
Structural Domains ◽  
Cellular Genes ◽  
Dna Binding Site ◽  
Discrete Domains ◽  
Definition Of ◽  
Site Recognition

GATA-3 is a zinc finger transcription factor which is expressed in a highly restricted and strongly conserved tissue distribution pattern in vertebrate organisms, specifically, in a subset of hematopoietic cells, in cells within the central and peripheral nervous systems, in the kidney, and in placental trophoblasts. Tissue-specific cellular genes regulated by GATA-3 have been identified in T lymphocytes and the placenta, while GATA-3-regulated genes in the nervous system and kidney have not yet been defined. We prepared monoclonal antibodies with which we could dissect the biochemical and functional properties of human GATA-3. The results of these experiments show some anticipated phenotypes, for example, the definition of discrete domains required for specific DNA-binding site recognition (amino acids 303 to 348) and trans activation (amino acids 30 to 74). The signaling sequence for nuclear localization of human GATA-3 is a property conferred by sequences within and surrounding the amino finger (amino acids 249 to 311) of the protein, thereby assigning a function to this domain and thus explaining the curious observation that this zinc finger is dispensable for DNA binding by the GATA family of transcription factors.

scholarly journals A cDNA for a human cyclic AMP response element-binding protein which is distinct from CREB and expressed preferentially in brain.

1990 ◽  
Vol 10 (4) ◽  
pp. 1347-1357 ◽  
Author(s):  
C J Kara ◽  
H C Liou ◽  
L B Ivashkiv ◽  
L H Glimcher
Keyword(s):  
Dna Binding ◽  
Cyclic Amp ◽  
Leucine Zipper ◽  
Binding Protein ◽  
Structural Similarity ◽  
Response Element ◽  
Cellular Genes ◽  
Viral Promoters ◽  
Element Binding Protein ◽  
Cyclic Amp Response Element

The cyclic AMP response element (CRE) is found in many cellular genes regulated by cyclic AMP, and similar elements are present in the early genes of adenovirus that are activated by E1A. The transcription factor CREB has previously been shown to bind this site, and cDNAs for CREB have recently been characterized. We report here the isolation of a cDNA encoding a human DNA-binding protein that also recognizes this motif in cellular and viral promoters. This protein, HB16, displays structural similarity to CREB and to c-Jun and c-Fos, which bind the related 12-O-tetradecanoylphorbol-13-acetate response element (TRE). HB16 contains a highly basic, putative DNA-binding domain and a leucine zipper structure thought to be involved in dimerization. Deletional analysis of HB16 demonstrated that the leucine zipper is required for its interaction with DNA. In addition, HB16 could form a complex with c-Jun but not with c-Fos. Despite its structural similarity to c-Jun and c-Fos and its interaction with c-Jun, HB16 had approximately a 10-fold-lower affinity for the TRE sequence than for the CRE sequence. Although HB16 and CREB both recognized the CRE motif, an extensive binding analysis of HB16 revealed differences in the fine specificity of binding of the two proteins. HB16 mRNA was found at various levels in many human tissues but was most abundant in brain, where its expression was widespread. The existence of more than one CRE-binding protein suggests that the CRE motif could serve multiple regulatory functions.

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