contributed equally to this work STAT factors act as signal transducers of cytokine receptors and transcriptionally activate speci®c target genes. The recently discovered protein PIAS3 binds directly to STAT3 and blocks transcriptional activation. Here, we present experimental evidence implementing the zinc ®nger protein G®-1 as a new regulatory factor in STAT3-mediated signal transduction. The interaction between the two proteins ®rst became evident in a yeast two-hybrid screen but was also seen in coprecipitation experiments from eukaryotic cells. Moreover, we found that both G®-1 and PIAS3 colocalize in a characteristic nuclear dot structure. While PIAS3 exerts a profound inhibitory effect on STAT3-mediated transcription of target promoters, G®-1 can overcome the PIAS3 block and signi®cantly enhances STAT3-mediated transcriptional activation. In primary T cells, G®-1 was able to amplify IL-6-dependent T-cell activation. As G®-1 is a known, dominant proto-oncogene, our ®ndings bear particular importance for the recently described ability of STAT3 to transform cells malignantly and offer an explanation of the oncogenic potential of G®-1 in T lymphocytes.
After rearrangement of the T-cell receptor (TCR)β-locus, early CD4 -/CD8 -double negative (DN) thymic T-cells undergo a process termed 'β-selection' that allows the preferential expansion of cells with a functional TCR β-chain. This process leads to the formation of a rapidly cycling subset of DN cells that subsequently develop into CD4 ϩ /CD8 ϩ double positive (DP) cells. Using transgenic mice that constitutively express the zinc finger protein Gfi-1 and the serine/threonine kinase Pim-1, we found that the levels of both proteins are important for the correct development of DP cells from DN precursors at the stage where 'β-selection' occurs. Analysis of the CD25 ϩ /CD44 -,lo DN subpopulation from these animals revealed that Gfi-1 inhibits and Pim-1 promotes the development of larger β-selected cycling cells ('L subset') from smaller resting cells ('E subset') within this subpopulation. We conclude from our data that both proteins, Pim-1 and Gfi-1, participate in the regulation of β-selection-associated pre-T-cell differentiation in opposite directions and that the ratio of both proteins is important for pre-T-cells to pass the 'E' to 'L' transition correctly during β-selection.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.