The Sp100 component of ND10/PML bodies is a potent tumor suppressor

The Sp100 component of ND10/PML bodies is a potent tumor suppressor: accelerated senescence and rapid malignant transformation of human fibroblasts through modulation of an embryonic stem cell program. Identifying the functions of proteins, which define specific subnuclear structures and territories, is important for understanding eukaryotic nuclear dynamics. Sp100 is a prototypical protein of ND10/PML bodies and colocalizes with the proto-oncogenic protein PML and Daxx, proteins with critical roles in oncogenic transformation, interferon-mediated viral resistance and response to PML-directed cancer therapeutics. Sp100 isoforms contain PHD, Bromo and HMG domains and are highly sumoylated at ND10/PML bodies, all characteristics suggestive of a role in chromatin mediated gene regulation. However, a clear role for Sp100 in oncogenesis has not been defined. Using isoform-specific knockdown techniques, we show that most human diploid fibroblasts, which lack Sp100, rapidly senesce. microarray analysis of mRNAs expression in BJV (collected at passage 47) and BJ-S (collected at passage 35). In addition, samples were treated for 24 h with 1000 U/ml IFNB. All RNAs were collected in triplicates of biological samples.