Ml clone S6 myeloid leukemic cells do not express detectable p53 protein. When stable transfected with a temperature-sensitive mutant of p53, these cells undergo rapid cell death upon induction of wild-type (wt) p53 activity at the permissive temperature. This process has features of apoptosis. In a number of other cell systems, wt p53 activation has been shown to induce a growth arrest. Yet, wt 53 fails to induce a measurable growth arrest in Ml cells, and cell cycle progression proceeds while viability is being lost. There exists, however, a relationship between the cell cycle and p53-mediated death, and cells in G, appear to be preferentially susceptible to the death-inducing activity of wt p53. In addition, p53-mediated Ml cell death can be inhibited by interleukin-6. The effect of the cytokine is specific to p53-mediated death, since apoptosis elicited by serum deprivation is refractory to interleukin-6. Our data imply that p53-mediated cell death is not dependent on the induction of a growth arrest but rather may result from mutually incompatible growthregulatory signals.The p53 phosphoprotein is the product of a tumor suppressor gene, whose inactivation may play a role in the development and progression of many types of cancer (reviewed in references 5, 26, 35, and 43). In most cases,

The acidic peroxidoxin [also named thiol-specific antioxidant protein (TSA) or protector protein (PRP)], which plays a role in the response against oxidative stress, is one of the major proteins of red blood cells. In this work, we show that this protein is induced at early stages of erythroid differentiation prior to haemoglobin accumulation, which suggests that it may play a role at the erythroblast stage, where haemoglobinized, nucleated and genetically active cells are submitted to a maximally dangerous oxidative stress. The early accumulation of this protein has been demonstrated both on transformed cell systems and on normal differentiating human erythroid cells. This suggests that this protein may play an important role in the differentiation of the erythroid cells.

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In this study we show a striking correlation between histone H1(0) gene expression and histone acetylation. Trichostatin A, a highly specific inhibitor of histone deacetylase, efficiently induces H1(0) gene expression. Moreover, using a cell line sensitive to trichostatin A (FM3A) and a derived cell line selected for its resistance to this inhibitor (TR303), it is shown that the level of H1(0) gene expression is related to the extent of chromatin acetylation. After showing the S-phase-dependent activation of H1(0) gene expression, we demonstrate that hyperacetylation has a dominant effect on H1(0) gene expression, since it enhances the expression of the gene independent of the position of cells in the cell cycle. This response to deacetylase inhibitors is specific to H1(0), since it is not shared by other cell-cycle-dependent histone genes (H1 and H4). Finally, by transfection of trichostatin-A-resistant and trichostatin-A-sensitive cells with a plasmid containing a H1(0) promoter, we show that the exogenous H1(0) promoter is also highly sensitive to trichostatin A treatment and that activation of transcription follows exactly the same pattern as activation of the endogenous gene. These data show that histone acetylation may be used to modulate H1(0) gene activity and offers insight into a possible mechanism in which the developmentally regulated chromatin acetylation acts to potentiate H1(0) gene expression.