|[교육과학기술부·한국연구재단 지정 한림대학교 생명공학연구소]
◎ 제6차 생명공학연구소 정기세미나 개최◎
Signaling Mechanisms of HIPK2 in Endoplasmic Reticulum Stress-induced Neuronal Death
이세범 박사(University of California)
A hallmark of many neurodegenerative diseases is the accumulation and deposits of abnormally folded proteins that activate signaling mechanisms leading to perturbation of neuronal functions and cell death. Accumulation of unfolded proteins in the endoplasmic reticulum (ER) lumen activates ER stress, which has been associated with a variety of neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS) and Parkinson’s disease (PD). However, the mechanisms of cell death activated by ER stress are not fully understood. In this study, we investigate the mechanism of HIPK2 (homeodomain interacting protein kinase 2), a member of the MAPKK family, in ER stress induced cell death. Our results show that HIPK2 is activated through ER membrane receptor tyrosine kinase (IRE1a) dependent mechanism. HIPK2 is not physically associated with IRE1a. Instead, ASK1 was found associated with both IRE1? and HIPK2. In fact, our subsequent results show that HIPK2 is downstream of ASK1 pathway. In addition, HIPK2 was required for JNK activation by ASK1. Since HIPK2 is an essential component in the ASK1-JNK pathway that is critical for ER stress-induced cell death, we tested if HIPK2 affect ER stress mediated apoptosis. To this end, we showed that HIPK2 regulates cell death by ER stress in mouse cortical neurons. To further characterize the in vivo functions of HIPK2 in ER stress-induced neurodegeneration, we used the SOD1 transgenic mouse model where ER stress has been implicated as a key mechanism for neuronal cell death. Consistent with the in vitro data with ER stress models, our preliminary results show that loss of HIPK2 delays motor neuron loss and disease onset in SOD1 transgenic mice. Together, our results demonstrate a previously unrecognized role of HIPK2 in the mechanisms of ER stress-induced cell death.
아래의 연사분을 초청하여 제 6차 정기세미나를 개최하오니 많은 참석 부탁드리겠습니다.
- 다 음-
▶ 일 시 : 2010. 06. 14(월) 오후 4시
▶ 장 소 : 산학협력단 세미나실(12102호)
▶ 연 자 : 이세범 박사(University of California)
▶ 주 최 : 생명공학연구소
▶ 연사 학력 및 경력
1994-2001 한림대학교 바이오메디컬학과 이학사
2002-2007 University of North Texas Ph.D.
2008-present University of California Postdoc