Fusion of One twenty-two to BSAC (Basic, SAP, and coiled-coil domain) results in aberrant upregulation of transcriptional activity

Authors:
Sawada T, Nishiyama C, Kishi T, Sasazuki T, Komazawa-Sakon S, Xue X, Piao JH, Ogata H, Nakayama JI, Taki T, Hayashi Y, Watanabe M, Yagita H, Okumura K, Nakano H
In:
Source: J Biol Chem
Publication Date: (2008)
Issue: epub: online
Research Area:
Cancer Research/Cell Biology
Immunotherapy / Hematology
Cells used in publication:
MEG-01
Species: human
Tissue Origin: bone marrow
Platform:
Nucleofectorâ„¢ I/II/2b
Abstract
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 Basic, SAP, and coiled-coil domain (BSAC) activates the promoters containing CArG boxes via interaction with serum response factor, and One twenty-two (OTT) 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 (YY)1-binding sequences. In addition, while 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 (HDAC)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.