Alteration of SMRT tumor suppressor function in transformed non-Hodgkin lymphomas.

Indolent non-Hodgkin lymphomas are characterized by a prolonged phase that is typically followed by a clinical progression associated with an accelerated clinical course and short survival time. Previous studies have not identified a consistent cytogenetic or molecular abnormality associated with transformation. The development of a transformed phenotype, evolving from the original low-grade component, most likely depends on multiple genetic events, including the activation of synergistic dominant oncogenes and a loss of tumor suppressor gene functions.

Activation of FoxO transcription factors contributes to the antiproliferative effect of cAMP.

cAMP is a potent inhibitor of cell proliferation in a variety of cell lines. Downregulation of cyclin D1 and upregulation of the cell cycle inhibitor p27Kip1 are two mechanisms by which cAMP may induce a G1-arrest. Here we show that cAMP inhibits proliferation of cells that constitutively express cyclin D1 or are deficient for Rb, demonstrating that changes in these cell cycle regulators do not account for the cAMP-induced growth effects in mouse embryo fibroblasts (MEFs).

FOXO transcription factor activation by oxidative stress mediated by the small GTPase Ral and JNK.

Forkhead transcription factors of the FOXO class are negatively regulated by PKB/c-Akt in response to insulin/IGF signalling, and are involved in regulating cell cycle progression and cell death. Here we show that, in contrast to insulin signalling, low levels of oxidative stress generated by treatment with H2O2 induce the activation of FOXO4. Upon treatment of cells with H2O2, the small GTPase Ral is activated and this results in a JNK-dependent phosphorylation of FOXO4 on threonine 447 and threonine 451.

HPV16 E6 and E7 oncoproteins regulate Notch-1 expression and cooperate to induce transformation.

Notch receptor signaling has been implicated in cellular transformation. Notch-1 receptor expression is increased during the progression from cervical intraepithelial lesions (CIN) to invasive cervical carcinoma. Moreover, the main cellular localization of Notch-1 protein changes from cytoplasmic to nuclear with the transition from CIN III to microinvasive carcinoma.

The Notch ligand Jagged-1 is able to induce maturation of monocyte-derived human dendritic cells.

Notch receptors play a key role in several cellular processes including differentiation, proliferation, and apoptosis. This study investigated whether the activation of Notch signaling would affect the maturation of dendritic cells (DCs). Direct stimulation of Notch signaling in DCs with a peptide ligand induced DC maturation, similar to LPS: DCs up-regulated maturation markers, produced IL-12, lost endocytosis capacity, and became able to activate allogeneic T cells.

Activation of Notch-1 signaling maintains the neoplastic phenotype in human Ras-transformed cells.

Truncated Notch receptors have transforming activity in vitro and in vivo. However, the role of wild-type Notch signaling in neoplastic transformation remains unclear. Ras signaling is deregulated in a large fraction of human malignancies and is a major target for the development of novel cancer treatments.