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B.S., Kyushu University, Japan
M.S., Osaka University, Japan
Ph.D., Osaka University, Japan
Post-Doctral, Thomas Jefferson University, Philadelphia, PA
Post-Doctral, Drexel University, Philadelphia, PA
Soft tissue clear cell sarcoma or malignant melanoma of soft parts is
rare and aggressive neuroectodermal tumor that occurs in the deep soft tissue usually
near tendons and aponeuroses. The recurrent t(12;22)(q13;q12) chromosomal translocation
associated with this sarcoma results in a chimeric protein EWS-ATF-1 that fuses putative
RNA-binding protein EWS to the CREB family transcriptional factor ATF-1. EWS-ATF-1
preserves amino-terminal regulatory domain of EWS and carboxyl-terminal half of ATF-1
including DNA-binding domain. We have shown that EWS-ATF-1 acts as a constitutive
transcriptional activator and that EWS-ATF-1 associates constitutively with coactivator
family CBP both in vitro and in vivo and represses p53/CBP-mediated trans-activation
function. These results suggest that targeting CBP/p300 by the aberrant fusion protein
EWS-ATF-1 may result in the altered function of tumor suppressor protein p53.
Ewing's sarcoma in which EWS gene and ETS gene are fused by aberrant chromosomal translocation
shows antiapoptotic activity against several inducers. In order to understand this
activity, we have created several deletion mutants and point mutants of Ewing's sarcoma
gene and analyzed viability against apoptotic inducers. we found that the transcriptional
deficient mutants including point mutant still retained the antiapoptotic activity.
Seeking alternative pathways, we found that this oncogene interact with transcriptional
cofactors and interfere its activity, which have pivotal roles in apoptosis.
- Cancer Biology focused on cancer stem cells. Mechanisms of Apoptosis.
- Functional aspects of cellular oncogenes/tumor supressor genes in Malignant melanoma
of soft parts, Ewing's sarcoma, and Prostate Cancer.
- Development of new method to analyse proteome of cancer.
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