TY - JOUR
T1 - Fusion of OTT to BSAC results in aberrant up-regulation of transcriptional activity
AU - Sawada, Taisuke
AU - Nishiyama, Chiharu
AU - Kishi, Takuma
AU - Sasazuki, Tomonari
AU - Komazawa-Sakon, Sachiko
AU - Xue, Xin
AU - Piao, Jiang Hu
AU - Ogata, Hideko
AU - Nakayama, Jun Ichi
AU - Taki, Tomohiko
AU - Hayashi, Yasuhide
AU - Watanabe, Mamoru
AU - Yagita, Hideo
AU - Okumura, Ko
AU - Nakano, Hiroyasu
PY - 2008/9/26
Y1 - 2008/9/26
N2 - OTT/RBM15-BSAC/MAL/MKL1/MRTF-A was identified as a fusion transcript generated by t(1;22)(p13;q13) in acute megakaryoblastic leukemia. Previous studies have shown that BSAC (basic, SAP, and coiled-coil domain) activates the promoters containing CArG boxes via interaction with serum response factor, and OTT (one twenty-two) negatively regulates the development of megakaryocytes and myeloid cells. However, the mechanism by which OTT-BSAC promotes leukemia is largely unknown. Here we show that OTT-BSAC, but not BSAC or OTT strongly activates several promoters containing a transcription factor Yin Yang 1-binding sequence. In addition, although BSAC predominantly localizes in the cytoplasm and its nuclear translocation is considered to be regulated by the Rho-actin signaling pathway, OTT-BSAC exclusively localizes in the nucleus. Moreover, OTT interacts with histone deacetylase 3, but this interaction is abolished in OTT-BSAC. Collectively, these functional and spatial changes of OTT and BSAC caused by the fusion might perturb their functions, culminating in the development of acute megakaryoblastic leukemia.
AB - OTT/RBM15-BSAC/MAL/MKL1/MRTF-A was identified as a fusion transcript generated by t(1;22)(p13;q13) in acute megakaryoblastic leukemia. Previous studies have shown that BSAC (basic, SAP, and coiled-coil domain) activates the promoters containing CArG boxes via interaction with serum response factor, and OTT (one twenty-two) negatively regulates the development of megakaryocytes and myeloid cells. However, the mechanism by which OTT-BSAC promotes leukemia is largely unknown. Here we show that OTT-BSAC, but not BSAC or OTT strongly activates several promoters containing a transcription factor Yin Yang 1-binding sequence. In addition, although BSAC predominantly localizes in the cytoplasm and its nuclear translocation is considered to be regulated by the Rho-actin signaling pathway, OTT-BSAC exclusively localizes in the nucleus. Moreover, OTT interacts with histone deacetylase 3, but this interaction is abolished in OTT-BSAC. Collectively, these functional and spatial changes of OTT and BSAC caused by the fusion might perturb their functions, culminating in the development of acute megakaryoblastic leukemia.
UR - http://www.scopus.com/inward/record.url?scp=55549123541&partnerID=8YFLogxK
U2 - 10.1074/jbc.M802315200
DO - 10.1074/jbc.M802315200
M3 - Article
C2 - 18667423
AN - SCOPUS:55549123541
SN - 0021-9258
VL - 283
SP - 26820
EP - 26828
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 39
ER -