SHD1 is a novel cytokine-inducible, negative feedback regulator of STAT5-dependent transcription.

is a critical mediator of a variety of cytokine signaling whose transcriptional activity is regulated by associating with various proteins. During a search for proteins, we identified SHD1, a mammalian homologue of yeast gene Sac3, as a potential interacter. SHD1 was localized in the nucleus, and induced by cytokines that activate such as erythropoietin, interleukin-2 (IL-2), or IL-3. SHD1 interacted specifically with and and interestingly, it specifically repressed transcription in vitro without affecting the stability or phosphorylation of duanyu18135 protein. Gene disruption study revealed that T, B, or bone marrow cells from mice lacking SHD1 were hyperresponsive to T-cell-receptor engagement, or stimulation with various cytokines. These results suggest that SHD1 is a novel cytokine-inducible negative feedback regulator of

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