STAT5 is a critical mediator of a variety of cytokine signaling whose transcriptional activity is regulated by associating with various proteins. During a search for STAT5-interacting 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 STAT5, such as erythropoietin, interleukin-2 (IL-2), or IL-3. SHD1 interacted specifically with STAT5A and STAT5B, and interestingly, it specifically repressed STAT5-dependent transcription in vitro without affecting the stability or phosphorylation of STAT5 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 STAT5-activating cytokines. These results suggest that SHD1 is a novel cytokine-inducible negative feedback regulator of STAT5.

中文翻译：

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SHD1 是一种新型的细胞因子诱导型，STAT5 依赖性转录的负反馈调节器

STAT5 是多种细胞因子信号传导的关键介质，其转录活性通过与各种蛋白质的结合进行调节。在寻找 STAT5 相互作用蛋白的过程中，我们将 SHD1（酵母基因 Sac3 的哺乳动物同源物）确定为潜在的相互作用者。SHD1 位于细胞核中，并由激活 STAT5 的细胞因子诱导，如促红细胞生成素、白细胞介素-2 (IL-2) 或 IL-3。SHD1 与 STAT5A 和 STAT5B 特异性相互作用，有趣的是，它在体外特异性抑制 STAT5 依赖性转录，而不影响 STAT5 蛋白的稳定性或磷酸化。基因破坏研究表明，来自缺乏 SHD1 的小鼠的 T、B 或骨髓细胞对 T 细胞受体结合或各种 STAT5 激活细胞因子的刺激有高反应性。