TY - JOUR
T1 - Physical and functional interactions between STAT3 and KAP1
AU - Tsuruma, R.
AU - Ohbayashi, N.
AU - Kamitani, S.
AU - Ikeda, O.
AU - Sato, N.
AU - Muromoto, R.
AU - Sekine, Y.
AU - Oritani, K.
AU - Matsuda, T.
N1 - Funding Information:
This study was supported in part by Sankyo Foundation of Life Science, Industrial Technology Research Grant Program in 2005 from New Energy and Industrial Technology Development Organization (NEDO) of Japan and Grant-in-Aid for scientific research from Ministry of Education, Culture, Sports, Science and Technology of Japan.
PY - 2008/5/8
Y1 - 2008/5/8
N2 - Signal transducers and activators of transcription (STATs) mediate cell proliferation, differentiation and survival in immune responses, hematopoiesis, neurogenesis and other biological processes. For example, STAT3 has been reported to be constitutively activated in numerous cancer cells. To clarify the molecular mechanisms underlying the STAT activation, we performed yeast two-hybrid screening and identified KAP1/TIF1β as a novel STAT-binding partner. KAP1 is a universal corepressor protein for the Kruppel-associated box zinc-finger protein superfamily of transcriptional repressors. We found endogenous KAP1 associated with endogenous STAT3 in vivo. Importantly, small-interfering RNA-mediated reduction of KAP1 expression enhanced interleukin (IL)-6-induced STAT3-dependent transcription and gene expression. Furthermore, reduction of KAP1 expression resulted in the marked accumulation of STAT3 phosphorylated on Ser727 in the nucleus, a modification that regulates its transcriptional activation. These results indicate that KAP1 may serve as a transcriptional regulator of the IL-6/STAT3 signaling pathway.
AB - Signal transducers and activators of transcription (STATs) mediate cell proliferation, differentiation and survival in immune responses, hematopoiesis, neurogenesis and other biological processes. For example, STAT3 has been reported to be constitutively activated in numerous cancer cells. To clarify the molecular mechanisms underlying the STAT activation, we performed yeast two-hybrid screening and identified KAP1/TIF1β as a novel STAT-binding partner. KAP1 is a universal corepressor protein for the Kruppel-associated box zinc-finger protein superfamily of transcriptional repressors. We found endogenous KAP1 associated with endogenous STAT3 in vivo. Importantly, small-interfering RNA-mediated reduction of KAP1 expression enhanced interleukin (IL)-6-induced STAT3-dependent transcription and gene expression. Furthermore, reduction of KAP1 expression resulted in the marked accumulation of STAT3 phosphorylated on Ser727 in the nucleus, a modification that regulates its transcriptional activation. These results indicate that KAP1 may serve as a transcriptional regulator of the IL-6/STAT3 signaling pathway.
KW - IL-6
KW - KAP1
KW - Phosphorylation
KW - STAT3
KW - Transcriptional regulation
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U2 - 10.1038/sj.onc.1210952
DO - 10.1038/sj.onc.1210952
M3 - Article
C2 - 18037959
AN - SCOPUS:43449110430
VL - 27
SP - 3054
EP - 3059
JO - Oncogene
JF - Oncogene
SN - 0950-9232
IS - 21
ER -
