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The oncogenic protein Ski associates with Smad proteins and counteracts their activation of gene expression and growth inhibition in response to transforming growth factor beta (TGF-beta). Here we show that Ski protein levels are increased in all 44 human melanoma tumor tissues analyzed in vivo. In addition, Ski subcellular localization changes from(More)
Genome modifications resulting from epigenetic changes appear to play a critical role in the development and/or progression of cancer. Scatter experimental evidence suggests that epigenetic changes could also be critical determinants of cellular senescence and organismal aging. Here we review the current evidence and discuss how imbalances in chromatin(More)
To understand the mechanism of interferon (IFN)-mediated suppression of cell cycle progression, we have earlier shown that IFN-alpha enhances the expression of underphosphorylated retinoblastoma protein by inhibiting the cyclin-dependent kinase-2 (CDK-2) activity (Kumar and Atlas, Proc. Natl. Acad. Sci. 89, 6599-6603, 1992; Zhang and Kumar, Biochem.(More)
Melanoma cells typically express wild-type p53, yet they are notoriously resistant to DNA-damaging agents. Here, we show that sodium butyrate (NaB), a histone deacetylase (HDAC) inhibitor, induced apoptosis in human melanoma cells in a dose- and time-dependent manner. Apoptosis was associated with HDAC1-dependent induction of Bax and acetylation of p53.(More)
Binding of extracellular ligands to epidermal growth factor receptors (EGFR) activate signal transduction pathways associated with cell proliferation, and these events are inhibited by monoclonal antibodies against EGFR. Since efficient DNA repair in actively growing cells may require growth factor signaling, it was of interest to explore any linkage(More)
Hormone-dependent breast cancer responds to primary therapies that block estrogen production or action, but tumor regrowth often occurs 12-18 months later. Additional hormonal treatments that further reduce estrogen synthesis or more effectively block its action cause additional remissions, but the mechanisms responsible for these secondary responses are(More)
The histone acetyltransferases p300 and cAMP-responsive element-binding protein-binding protein (CBP) are required for the execution of critical biological functions such as proliferation, differentiation, and apoptosis. Both proteins are believed to regulate the activity of a large number of general and cell-specific transcription factors. Here we(More)
Cancer cells have abnormal cell cycle regulation which favors accelerated proliferation, chromosomal instability, and resistance to the senescence response. Although the p16INK4a locus is the most prominent susceptibility locus for familial melanomas, the low frequency of p16 mutations in sporadic melanomas suggests additional alterations in other cell(More)
The retinoblastoma (RB)/p16(INK4a) pathway regulates senescence of human melanocytes in culture and oncogene-induced senescence of melanocytic nevi in vivo. This senescence response is likely due to chromatin modifications because RB complexes from senescent melanocytes contain increased levels of histone deacetylase (HDAC) activity and tethered HDAC1. Here(More)
The melanocyte is a neural crest-derived cell that localizes in humans to several organs including the epidermis, eye, inner ear and leptomeninges. In the skin, melanocytes synthesize and transfer melanin pigments to surrounding keratinocytes, leading to skin pigmentation and protection against solar exposure. We have investigated the process of replicative(More)