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

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 co-localizes 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, no clear role for the Sp100 component of PML bodies in oncogenesis has been defined. Using isoform-specific knockdown techniques, we show that most human diploid fibroblasts, which lack Sp100, rapidly senesce and discuss gene expression changes associated with this rapid senescence. 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.