Following transplantation of hematopoietic lineage cells, genetic markers unique to the transplanted cells have been detected in non-hematopoietic recipient cells of human liver, vascular endothelium, intestinal epithelium and brain. The underlying mechanisms by which this occurs are unclear. Evidence from mice suggests it is due in part to fusion between cells of hematopoietic and non-hematopoietic origins; however, direct evidence for this in humans is scant.
View Article and Find Full Text PDFp53 is a unique DNA binding protein with two distinct DNA binding domains, the central domain for sequence-specific DNA binding and the C-terminal basic DNA binding domain (BD domain) for structure-specific DNA binding. In contrast to the apparent inhibitory effect of the BD domain on p53 binding to sequence-specific DNA in vitro, here we demonstrate that the BD domain enhances p53 binding to the endogenous p21(Waf1) promoter and mediates rapid transactivation of p21.(Waf1) This paradox is resolved by the observation that the BD domain is required for rapid binding to non-sequence-specific genomic DNA (NS-DNA) as evident from global chromatin immunoprecipitation analysis of p53 DNA binding in vivo.
View Article and Find Full Text PDFTripartite motif protein 32, Trim32, mRNA and protein expression was elevated in independently transformed and tumorigenic keratinocytes of a mouse epidermal carcinogenesis model, in ultraviolet B (UVB)-induced squamous cell carcinomas (SCC), and in approximately 20-25% of chemically induced mouse papillomas and human head and neck SCCs. This suggests that elevated Trim32 expression occurs frequently in experimental epidermal carcinogenesis and is relevant to human cancer. Transduced Trim32 increased colony number in an epidermal in vitro transformation assay and epidermal thickening in vivo when skin-grafted to athymic nu/nu mice.
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