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I Pirson

Publications and source records attributed to I Pirson.

24 records · Page 2Linked to original sources
PubMed1994

Highly sensitive control of transcriptional activity by factor heterodimerization.

Several molecular mechanisms have been proposed to explain highly sensitive controls of cellular functions by effector molecules. Here we study an equilibrium model describing the regulation of transcriptional activity through the heterodimerization of transcription factors. We demonstrate that this model involves a new type of biochemical control which accounts for a very high sensitivity.

Basic-Leucine Zipper Transcription Factors↗
PubMed1994

Regulation of the Max gene expression by different mitogenic pathways in dog primary thyrocytes.

The family of Myc proteins appears to function through heterodimerization with the bHLH-Zip protein Max. We have investigated the regulation of Max mRNA in primary cultured dog thyrocytes whose proliferation is stimulated by three distinct mitogenic pathways: (1) the thyrotropin (TSH) cascade mediated by cyclic AMP, (2) the protein kinase C pathway activated by diacylglycerol and phorbol esters such as 12-O-tetradecanoylphorbol 13-acetate (TPA), (3) a protein tyrosine kinase system activated by epidermal growth factor (EGF). Among these cascades only the first is compatible with differentiation. We have observed that the mRNA of Max is stable and regulated differentially by the three pathways in our system. TSH decreases the level of the messenger while EGF or TPA increases it with early delayed kinetics. The effect of cyclic AMP on the accumulation of Max is observed even in the presence of cycloheximide, while the EGF- or TPA-induced increase is cycloheximide sensitive, suggesting differences in regulation pathways. Max mRNA is regulated with the same intensity, but in a more delayed fashion than the messenger of c-myc. As Max protein mediates the transcriptional effects of c-Myc our results are compatible with a mediator role of Max in modulating the cell sensitivity to the proliferative signal c-Myc.

Animals↗
PubMed1994

Jun B expression is regulated differently by three mitogenic pathways in thyrocytes.

In dog thyrocytes in primary culture, thyrotropin (TSH), acting through cyclic AMP, induces proliferation and differentiation expression, while tetradecanoylphorbol acetate (TPA) or epidermal growth factor (EGF) induces proliferation and dedifferentiation. In this work, we have investigated the regulation of mRNA expression of the protooncogene jun B in these cells. TSH stimulated jun B expression very transiently with biphasic kinetics similar to those obtained for c-myc mRNA accumulation. Forskolin reproduced these effects, suggesting that they are, as other effects of TSH in this system, mediated by cyclic AMP. As shown by nuclear run-on experiments, jun B is regulated by the cAMP pathway at the transcriptional level. As in other cell types, EGF or TPA caused a more sustained increase in mRNA levels. In thyroid slices, in which DNA synthesis appears to be induced by the wounding process, jun B is also induced, suggesting a correlation with the proliferative status of the cell. Interestingly, two jun B mRNAs of 2.1 and 2.3 kb were induced by all the mitogenic pathways. The kinetics of their accumulation were different; i.e., TPA induced the smaller transcript with some delay after the longer one and cycloheximide induced the progressive shortening of the first appearing heavier mRNA. The 2.3-kb messenger has a longer poly(A) tail, and kinetics in the presence of actinomycin D suggested it could represent a precursor form of the 2.1-kb messenger. It is suggested that the specific kinetics of cyclic-AMP-induced accumulation of jun B mRNA could be related to the dual stimulation of differentiation and proliferation by TSH in dog thyrocytes.

Animals↗
PubMed1991

Differential regulation of protooncogenes c-jun and jun D expressions by protein tyrosine kinase, protein kinase C, and cyclic-AMP mitogenic pathways in dog primary thyrocytes: TSH and cyclic-AMP induce proliferation but downregulate C-jun expression.

The expressions of the protooncogenes c-jun and jun D have been investigated in dog thyrocytes in a primary culture whose proliferation is stimulated by three distinct intracellular signaling pathways (1) the thyrotropin (TSH) or forskolin-cyclic-AMP-mediated cascade; (2) the protein kinase C pathway activated by diacylglycerol (DAG) and phorbol esters (TPA); (3) a protein tyrosine kinase system activated by epidermal growth factor (EGF). While the first cascade is compatible with the differentiated state of the cell, the two latter pathways induce dedifferentiation. Following the stimulation by TPA or EGF, the expression of c-jun was increased and the expression of jun D was faintly increased. Both expressions are superinduced in the presence of cycloheximide as in mitogenically stimulated fibroblasts but, in the presence of cycloheximide alone, the expressions of c-jun and jun D are clearly unstable with time. This indicates that cycloheximide controls should be included at all time points examined in such experiments. Increasing intracellular concentrations of cyclic-AMP by forskolin or TSH was followed by an inhibition of the expression of c-jun. This inhibition was independent of protein synthesis. Similarly, the TPA or EGF stimulation of c-jun expression was also inhibited by TSH or forskolin, as in fibroblasts in which cyclic-AMP inhibits proliferation. Our results show that the expression of c-jun is not universally correlated with the stimulation of cell proliferation. The stimulation of c-jun expression is not common between the three mitogenic pathways. It thus represents another of the very different responses elicited by the cyclic-AMP cascade as compared to the more studied tyrosine kinase and protein kinase C mitogenic pathways.

Animals↗
PubMed1991

The TSH cyclic AMP cascade in the control of thyroid cell proliferation: the story of a concept.

Thyrotropin stimulates the growth and proliferation of thyroid cells in vivo. Starting in the 1970, we have progressively shown that these effects could be reproduced in vitro in dog thyroid cells in primary culture. They are accompanied by the expression of differentiation. All the effects of thyrotropin are mediated by the cyclic AMP cascade. The best argument that this concept applies in vivo is the generation of hyperfunctioning adenoma involving the whole gland in transgenic mice expressing the constitutively active adenosine A2 receptor in the thyroid.

Animals↗