scholarly journals Stimulation of DNA synthesis by natural ceramide 1-phosphate

1997 ◽  
Vol 325 (2) ◽  
pp. 435-440 ◽  
Author(s):  
Antonio GOMEZ-MUÑOZ ◽  
Laura M. FRAGO ◽  
Luis ALVAREZ ◽  
Isabel VARELA-NIETO
Keyword(s):  
Dna Synthesis ◽  
Proliferating Cell Nuclear Antigen ◽  
Solvent Mixture ◽  
Mitogen Activated Protein Kinase ◽  
Nuclear Antigen ◽  
Tyrosine Residues ◽  
Mitogen Activated Protein ◽  
Ceramide 1 ◽  
Proliferating Cell ◽  
Stimulation Of

We found that natural (long-chain) ceramide 1-phosphate can be dispersed into aqueous solution when dissolved in an appropriate mixture of methanol/dodecane (49:1, v/v). This solvent mixture facilitates the interaction of this phosphosphingolipid with cells. Under these conditions, incubation of EGFR T17 fibroblasts with natural ceramide 1-phosphate caused a potent stimulation of DNA synthesis. This effect was accompanied by an increase in the levels of proliferating-cell nuclear antigen. Concentrations of natural ceramide 1-phosphate that stimulated the synthesis of DNA did not inhibit adenylate cyclase activity, nor did they stimulate phospholipase D. Natural ceramide 1-phosphate did not alter the cellular phosphorylation state of tyrosine residues or of mitogen-activated protein kinase. Furthermore, natural ceramide 1-phosphate failed to induce the expression of the proto-oncogenes c-myc and c-fos. Both the stimulation of DNA synthesis and the induction of proliferating-cell nuclear antigen by natural ceramide 1-phosphate were inhibited by natural ceramides. This work suggests that the use of methanol and dodecane to deliver natural ceramide 1-phosphate to cells may be useful for elucidation of the biological function(s) and mechanism(s) of action of ceramide 1-phosphate.

Different functional domains of the adenovirus E1A gene are involved in regulation of host cell cycle products

1987 ◽  
Vol 7 (2) ◽  
pp. 821-829
Author(s):  
B Zerler ◽  
R J Roberts ◽  
M B Mathews ◽  
E Moran
Keyword(s):  
Cell Cycle ◽  
Dna Synthesis ◽  
Proliferating Cell Nuclear Antigen ◽  
Nuclear Antigen ◽  
Deletion Mutants ◽  
Terminal Exon ◽  
Adenovirus E1a ◽  
E1a Gene ◽  
Proliferating Cell ◽  
Stimulation Of

We have analyzed the cell cycle effects that different domains of the adenovirus E1A proteins have on quiescent primary BRK cells. Studies with deletion mutants that in combination removed all but the N-terminal 85 amino acids common to both the 12S and 13S proteins suggest that this region may be sufficient for the induction of synthesis of proliferating cell nuclear antigen and the stimulation of DNA synthesis. A second domain also common to the N-terminal exon of the 12S and 13S proteins was required for the induction of mitosis and stimulation of proliferation of primary BRK cells. A virus containing a mutation in this region was still able to stimulate DNA synthesis efficiently. A third domain, unique to the 13S protein, was required for the accelerated activation of the cellular thymidylate synthase gene in a manner similar to the 13S-dependent stimulation of adenovirus early region genes.

scholarly journals Different functional domains of the adenovirus E1A gene are involved in regulation of host cell cycle products.

1987 ◽  
Vol 7 (2) ◽  
pp. 821-829 ◽  
Author(s):  
B Zerler ◽  
R J Roberts ◽  
M B Mathews ◽  
E Moran
Keyword(s):  
Cell Cycle ◽  
Dna Synthesis ◽  
Proliferating Cell Nuclear Antigen ◽  
Nuclear Antigen ◽  
Deletion Mutants ◽  
Terminal Exon ◽  
Adenovirus E1a ◽  
E1a Gene ◽  
Proliferating Cell ◽  
Stimulation Of

We have analyzed the cell cycle effects that different domains of the adenovirus E1A proteins have on quiescent primary BRK cells. Studies with deletion mutants that in combination removed all but the N-terminal 85 amino acids common to both the 12S and 13S proteins suggest that this region may be sufficient for the induction of synthesis of proliferating cell nuclear antigen and the stimulation of DNA synthesis. A second domain also common to the N-terminal exon of the 12S and 13S proteins was required for the induction of mitosis and stimulation of proliferation of primary BRK cells. A virus containing a mutation in this region was still able to stimulate DNA synthesis efficiently. A third domain, unique to the 13S protein, was required for the accelerated activation of the cellular thymidylate synthase gene in a manner similar to the 13S-dependent stimulation of adenovirus early region genes.

Demonstration of cell cycle kinetics in thyroid primary culture by immunostaining of proliferating cell nuclear antigen: differences in cyclic AMP-dependent and -independent mitogenic stimulations

1993 ◽  
Vol 105 (1) ◽  
pp. 69-80 ◽  
Author(s):  
M. Baptist ◽  
J.E. Dumont ◽  
P.P. Roger
Keyword(s):  
Cell Cycle ◽  
Dna Synthesis ◽  
Primary Culture ◽  
Proliferating Cell Nuclear Antigen ◽  
Cell Cycle Progression ◽  
Nuclear Antigen ◽  
Major Influence ◽  
Cell Cycle Kinetics ◽  
Experimental Conditions ◽  
Proliferating Cell

In this study, experimental conditions are described that allowed us to follow the fate of the DNA polymerase delta-associated proliferating cell nuclear antigen (PCNA), by immunolabeling during the overall cell cycle. Differences in subcellular localization or the presence of PCNA allowed us to identify each phase of the cell cycle. Using these cell cycle markers in dog thyroid epithelial cells in primary culture, we found unexpected differences in cell cycle kinetics, in response to stimulations through cAMP-dependent and cAMP-independent pathways. These provide a new dimension to the view that the two pathways are largely separate, but co-operate on DNA synthesis initiation. More precisely, thyrotropin (TSH), acting via cAMP, exerts a potent triggering effect on DNA synthesis, associated with a precocious induction of PCNA appearance. This constitutes the major influence of TSH (cAMP) in determining cell cycle progression, which is only partly moderated by TSH-dependent lengthening of S- and G2-phases.

Dual mode of interaction of DNA polymerase ϵ with proliferating cell nuclear antigen in primer binding and DNA synthesis 1 1Edited by J. Karn

1999 ◽  
Vol 285 (1) ◽  
pp. 259-267 ◽  
Author(s):  
Giovanni Maga ◽  
Zophonı́as O Jónsson ◽  
Manuel Stucki ◽  
Silvio Spadari ◽  
Ulrich Hübscher
Keyword(s):  
Dna Synthesis ◽  
Dna Polymerase ◽  
Proliferating Cell Nuclear Antigen ◽  
Nuclear Antigen ◽  
Dual Mode ◽  
Proliferating Cell

scholarly journals Functional Interactions of a Homolog of Proliferating Cell Nuclear Antigen with DNA Polymerases inArchaea

1999 ◽  
Vol 181 (21) ◽  
pp. 6591-6599 ◽  
Author(s):  
Isaac K. O. Cann ◽  
Sonoko Ishino ◽  
Ikuko Hayashi ◽  
Kayoko Komori ◽  
Hiroyuki Toh ◽  
...  
Keyword(s):  
Dna Replication ◽  
Dna Synthesis ◽  
Proliferating Cell Nuclear Antigen ◽  
Dna Polymerases ◽  
Nuclear Antigen ◽  
Pol Ii ◽  
Circular Dna ◽  
Pol I ◽  
Factor C ◽  
Proliferating Cell

ABSTRACT Proliferating cell nuclear antigen (PCNA) is an essential component of the DNA replication and repair machinery in the domainEucarya. We cloned the gene encoding a PCNA homolog (PfuPCNA) from an euryarchaeote, Pyrococcus furiosus, expressed it in Escherichia coli, and characterized the biochemical properties of the gene product. The protein PfuPCNA stimulated the in vitro primer extension abilities of polymerase (Pol) I and Pol II, which are the two DNA polymerases identified in this organism to date. An immunological experiment showed that PfuPCNA interacts with both Pol I and Pol II. Pol I is a single polypeptide with a sequence similar to that of family B (α-like) DNA polymerases, while Pol II is a heterodimer. PfuPCNA interacted with DP2, the catalytic subunit of the heterodimeric complex. These results strongly support the idea that the PCNA homolog works as a sliding clamp of DNA polymerases in P. furiosus, and the basic mechanism for the processive DNA synthesis is conserved in the domainsBacteria, Eucarya, and Archaea. The stimulatory effect of PfuPCNA on the DNA synthesis was observed by using a circular DNA template without the clamp loader (replication factor C [RFC]) in both Pol I and Pol II reactions in contrast to the case of eukaryotic organisms, which are known to require the RFC to open the ring structure of PCNA prior to loading onto a circular DNA. Because RFC homologs have been found in the archaeal genomes, they may permit more efficient stimulation of DNA synthesis by archaeal DNA polymerases in the presence of PCNA. This is the first stage in elucidating the archaeal DNA replication mechanism.

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