연구논문

세부과제번호 2014M3A9D5A01073789 단계 1단계 3차년도
세부과제명 마우스 면역 질환표현형 분석 기반구축 공동 유/무 -
SCI여부 Y 게재년월 2016-7
논문제목 Expression of Twist2 is controlled by T-cell receptor signaling and determines the survival and death of thymocytes.
총저자명 S OhJ OhC LeeS OhS JeonJ ChoiS HwangY LeeH LeeR H Seong
학술지명 Cell Death Differ. 게재권(호) ()
저널구분 - 페이지수 -
참여연구원 성노현 연구책임자 성노현
과제기여도 30 PMID 27391798
사사기관수 - IF (년도) 8.184
제1저자 오상욱 교신저자 성노현
공동저자 -
초록
Self-reactive thymocytes are eliminated by negative selection, whereas competent thymocytes survive by positive selection. The strength of the T-cell receptor (TCR) signal determines the fate of thymocytes undergoing either positive or negative selection. The TCR signal strength is relatively higher in negative selection than in positive selection and induces pro-apoptotic molecules such as Nur77 and Nor-1, which are members of the orphan nuclear receptor family, that then cause TCR-mediated apoptosis. However, at the molecular level, it remains unclear how positive or negative selection is distinguished based on the TCR signal. We found that the expression of Twist2 is differentially regulated in positively and negatively selected thymocytes. In particular, TCR signal strength that elicits positive selection induces Twist2 expression via the Ca(2+)-Cacineurin-NFATc3 pathway, whereas strength of the TCR signal that results in negative selection abolishes NFATc3-dependent Twist2 induction via specific activation of the JNK pathway. Using Twist2-deficient and Twist2 transgenic mice, we also found that Twist2 determines thymocyte sensitivity to TCR-mediated apoptosis by regulating the expression of Nur77 and Nor-1. Twist2 partially retains histone deacetylase 7 (HDAC7) in the nucleus and recruits it to the Nur77 promoter region to repress Nur77 in positively selected thymocytes. Thus our results suggest a molecular mechanism of how thymocytes interpret the strength of the TCR signal and how TCR sensitivity is controlled during thymic selection.Cell Death and Differentiation advance online publication, 8 July 2016; doi:10.1038/cdd.2016.68.
다음글
이전글