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

First Author  Nakajima H Year  2009
Journal  Blood Volume  113
Issue  5 Pages  1027-36
PubMed ID  18838617 Mgi Jnum  J:144601
Mgi Id  MGI:3831260 Doi  10.1182/blood-2008-01-133405
Citation  Nakajima H, et al. (2009) SHD1 is a novel cytokine-inducible, negative feedback regulator of STAT5-dependent transcription. Blood 113(5):1027-36
abstractText  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.
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