TY - JOUR
T1 - SHD1 is a novel cytokine-inducible, negative feedback regulator of STAT5-dependent transcription
AU - Nakajima, Hideaki
AU - Tamura, Toshiki
AU - Ito, Miyuki
AU - Shibata, Fumi
AU - Kuroda, Kana
AU - Fukuchi, Yumi
AU - Watanabe, Naohide
AU - Kitamura, Toshio
AU - Ikeda, Yasuo
AU - Handa, Makoto
PY - 2009/1/29
Y1 - 2009/1/29
N2 - 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.
AB - 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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U2 - 10.1182/blood-2008-01-133405
DO - 10.1182/blood-2008-01-133405
M3 - Article
C2 - 18838617
AN - SCOPUS:60849089909
SN - 0006-4971
VL - 113
SP - 1027
EP - 1036
JO - Blood
JF - Blood
IS - 5
ER -