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Phosphorylation of p53 at Ser 46 was shown to regulate p53 apoptotic activity. Here we demonstrate that homeodomain-interacting protein kinase-2 (HIPK2), a member of a novel family of nuclear serine/threonine kinases, binds to and activates p53 by directly phosphorylating it at Ser 46. HIPK2 localizes with p53 and PML-3 into the nuclear bodies and is(More)
The interaction of integrins with extracellular matrix is known to promote cell survival by inhibiting apoptotic signaling. In contrast, we demonstrate here that the alpha6beta4 integrin induces apoptosis in carcinoma cells by stimulating p53 function. Specifically, we show that expression of alpha6beta4 in carcinoma cells that lack this integrin stimulates(More)
Most genes are members of a family. It is generally believed that a gene family derives from an ancestral gene by duplication and divergence. The tumor suppressor p53 was a striking exception to this established rule. However, two new p53 homologs, p63 and p73, have recently been described [1-6]. At the sequence level, p63 and p73 are more similar to each(More)
The p53 tumor suppressor gene is activated in response to DNA damage resulting in either growth arrest or apoptosis. We previously demonstrated the specific involvement of homeodomain interacting protein-kinase 2 (HIPK2), a nuclear serine/threonine kinase, in inducing p53-dependent apoptosis through selective p53 phosphorylation at serine 46 after severe(More)
Different cell types (e.g., neurons, skeletal and heart myocytes, adipocytes, keratinocytes) undergo terminal differentiation, in which acquisition of specialized functions entails definitive withdrawal from the cell cycle. Such cells are distinct from quiescent (reversibly growth-arrested) cells, such as contact-inhibited fibroblasts. Terminally(More)
Mutations in the methyl-CpG-binding protein 2 (MeCP2) are associated with Rett syndrome and other neurological disorders. MeCP2 represses transcription mainly by recruiting various co-repressor complexes. Recently, MeCP2 phosphorylation at Ser 80, Ser 229 and Ser 421 was shown to occur in the brain and modulate MeCP2 silencing activities. However, the(More)
Although the interaction of matrix proteins with integrins is known to initiate signaling pathways that are essential for cell survival, a role for tumor suppressors in the regulation of these pathways has not been established. We demonstrate here that p53 can inhibit the survival function of integrins by inducing the caspase-dependent cleavage and(More)
Galectin 3 (Gal-3), a member of the beta-galactoside binding lectin family, exhibits antiapoptotic functions, and its aberrant expression is involved in various aspects of tumor progression. Here we show that p53-induced apoptosis is associated with transcriptional repression of Gal-3. Previously, it has been reported that phosphorylation of p53 at Ser46 is(More)
Stimulation of the Ras/MAPK cascade can either activate p53 and promote replicative senescence and apoptosis, or degrade p53 and promote cell survival. Here we show that p53 can directly counteract the Ras/MAPK signaling by inactivating ERK2/MAPK. This inactivation is due to a caspase cleavage of the ERK2 protein and contributes to p53-mediated growth(More)
We have analyzed by immunocytochemistry (ICC) the frequency of p53 protein expression in 181 cases of B-cell chronic lymphocytic leukemia (CLL) followed at a single institution to assess the relationship between p53 and the clinical and morphological features of the disease, as well as the possible involvement of this protein in the pathogenesis of the more(More)