Abstract:
본 발명은 TFG-TEC 융합 단백질의 신규한 전사활성능 및 전이활성능을 이용한 종양 질환의 예방 또는 치료용 물질의 스크리닝 방법 및 이의 약제학적 조성물, 그리고 TFG(NTD)를 이용한 전사활성 촉진용 발현 벡터 및 조성물을 제공한다. 본 발명의 TFG-TEC 융합 단백질은 TEC와 동일한 서열 특이성을 가질 뿐 아니라, TEC보다 더욱 우수한 전사활성 촉진능을 가진다. 또한, 본 발명의 TFG-TEC 융합 단백질 내 TFG(NTD)는 강력한 전이활성 도메인(transactivation domain)으로 기능하고, 상기 TFG(NTD)의 PB1 도메인 및 SPYGQ-풍부 부위(SPYGQ-rich regions)가 부분적인 전이활성(partial transactivation)을 가진다. 그 결과, 본 발명의 TFG-TEC 융합 단백질은 TEC에 의해 조절받는 것으로 알려진 다운스트림 유전자들(예컨대, Skp2 , L- Myc , SOCS2 또는 STAT -3 )의 발현을 촉진시킨다. 따라서, TFG-TEC 융합 유전자의 발현을 억제시키거나 또는 TFG-TEC 융합 단백질의 활성을 억제시키는 물질에 대한 스크리닝 방법 및 이를 이용한 약제학적 조성물은 종양 질환, 질병 또는 상태의 예방 또는 치료에 유용하게 적용될 수 있다.
Abstract:
The present invention provides a method for screening a material for preventing or treating tumor diseases using novel transcription activating functions and transactivation functions of a TFG-TEC fusion protein, a pharmaceutical composition of the same, and an expression vector and a composition for promoting transcription activities using TFG (NTD). The TFG-TEC fusion protein of the present invention not only has the same sequence specificity as TEC, but also has more excellent transcription activation promoting functions than TEC. Moreover, the TFG (NTD) in the TFG-TEC fusion protein of the present invention serves as a strong transactivation domain, and PB1 domains and SPYGQ-rich regions of the TFG (NTD) have partial transactivation. As a result, the TFG-TEC fusion protein of the present invention promotes the expression of downstream genes (e.g. Skp2, L-Myc, SOCS2, or STAT-3) which are known to be regulated by TEC. Accordingly, the method for screening a material which inhibits the expression of a TFG-TEC fused gene or inhibits the activation of a TFG-TEC fusion protein and the pharmaceutical composition using the same can be usefully applied in preventing or treating tumor diseases.
Abstract:
The present invention provides a method for screening a substance for preventing or treating tumor disorders using novel transcriptional activation and transactivation of the TFG-TEC fusion protein, a pharmaceutical composition thereof, and an expression vector and a composition for promoting transcriptional activity using TFG (NTD). The TFG-TEC fusion protein of the present invention has identical sequence specificity to the TEC, and more excellent ability to promote transcriptional activity. In addition, the TFG (NTD) in the TFG-TEC fusion protein of the present invention functions as a transactivation domain, and the PB1 domain and SPYGQ-rich regions of the TFG (NTD) has partial transactivation. As a result, the TFG-TEC fusion protein of the present invention promotes the expression of downstream genes (e.g., Skp2, L-Myc, SOCS2, or STAT-3), which has been known to be regulated by TEC. Thus, the method for screening a substance for inhibiting the expression of the TFG-TEC fusion protein or inhibit the activity of the TFG-TEC fusion protein and the pharmaceutical composition using the same can be useful to prevent or treat tumor disorders, diseases, or conditions.