Sp110 localizes to the PML-Sp100 nuclear body and may function as a nuclear hormone receptor transcriptional coactivator

The nuclear body is a multiprotein complex that may have a role in the regu lation of gene transcription. This structure is disrupted in a variety of h uman disorders including acute promyelocytic leukemia and viral infections, suggesting that alterations in the nuclear body mag have an important role in the pathogenesis of these diseases. In this study, we identified a cDNA encoding a leukocyte-specific nuclear body component designated Sp110, The N-terminal portion of Sp110 was homologous to two previously characterized components of the nuclear body (Sp100 and Sp140). The C-terminal region of Sp110 was homologous to the transcription intermediary factor 1 (TIF1) fam ily of proteins. High levels of Sp110 mRNA were detected in human periphera l blood leukocytes and spleen but not in other tissues, The levels of Sp110 mRNA and protein in the human promyelocytic leukemia cell line NB4 increas ed following treatment with all-trans retinoic acid (ATRA), and Sp110 local ized to PML-Sp100 nuclear bodies in ATRA-treated NB4 cells. Because of the structural similarities between Sp110 and TIF1 proteins, the effect of Sp11 0 on gene transcription was examined. An Sp110 DNA-binding domain fusion pr otein activated transcription of a reporter gene in transfected mammalian c ells. In addition, Sp110 produced a marked increase in ATRA-mediated expres sion of a reporter gene containing a retinoic acid response element. Taken together, the results of this study demonstrate that Sp110 is a member of t he Sp100/Sp140 family of nuclear body components and that Sp110 may functio n as a nuclear hormone receptor transcriptional coactivator. The predominan t expression of Sp110 in Leukocytes and the enhanced expression of Sp110 in NB4 cells treated with ATRA raise the possibility that Sp110 has a role in inducing differentiation of myeloid cells.