|[교육과학기술부·한국연구재단 지정 한림대학교 생명공학연구소]
◎ 제18차 생명공학연구소 정기세미나 개최 ◎
▶ 일 시 : 2012. 11. 9(금) 오전 11시
▶ 장 소 : 산학협력단 세미나실(12102호)
▶ 연 자 : 김경현 박사(Univ. Cincinnati)
▶ 주 최 : 생명공학연구소
▶ 강의제목 : SPECIFICITY PROTEINS LINK ONCOGENIC MICRORNA-ZBTB4 SIGNALING AXIS TO EZH2 REGULATION.
The Enhancer of Zeste 2 (EZH2) protein is a histone methyltransferase that mediates epigenetic silencing through chromatin remodeling. EZH2 plays a pivotal role in cell self-renewal and tumorigenesis and is frequently overexpressed in many cancers. Thus, it is important to identify pathways that regulate EZH2 expression and to develop therapeutic strategies to target EZH2. Oncogenic microRNAs (miRs), including miR-106b and miR-93, target ZBTB4 which functions as Specificity proteins (Sps) repressor through competitive binding to GC-rich sequences. Increased ZBTB4 expression by oncogenic miR depletion resulted in downregulation of Sp1, Sp3 and Sp4 proteins and Sp-dependent oncogenes, including survivin, VEGF and VEGFR1, suggesting a tumor suppressive role for ZBTB4. Bioinformatics analysis result further revealed that EZH2 is a downstream target of ZBTB4 and in fact, ZBTB4 overexpression repressed EZH2 expression through downregulation of Sp proteins in MCF-7 and MDA-MB-231 breast cancer cells. Sp1, Sp3 and Sp4 knockdown by RNA interference decreased EZH2, indicating that Sp proteins are necessary for EZH2 expression. Chromatin immunoprecipitation and gel shift assays confirmed that Sp proteins bound GC-rich Sp binding sites on the EZH2 promoter and ZBTB4 compete Sp protein binding at these sites. Furthermore, transfection of miR-106b antagomiR increased ZBTB4 and decreased EZH2 expression and this was accompanied by enhanced ZBTB4 binding to the GC-rich sites in the EZH2 gene promoter. Moreover, betulinic acid (BA), a phytochemical previously reported to downregulateSp proteins in various cancer cell lines also decreased EZH2 expression by modulating the oncogenic miR/ZBTB4 axis. These results underscore Sps as “non-oncogene addiction“ proteins essential to maintain oncogene function and cancer phenotype during tumorigenesis. Furthermore, this is the first study showing that Sp proteins connect oncogenic miR-ZBTB4 pathway to EZH2 regulation and that inhibition of Sp proteins by BA will be a novel therapeutic approach that targets EZH2.
▶ 연사 학력 및 경력
1993 Hallym University Department of Genetic Engineering B.S.
1997 Rutgers University Department of Cell & Developmental Biology M.S.
2004 Texas A&M University Department of Toxicology Ph.D.
2004-2005 Texas A&M University Postdoctoral Fellow
2005-2006 UC San Diego Postdoctoral Research Associate
2007-2008 UT MD Anderson Cancer Center Postdoctoral Research Associate
2009-2012 Texas A&M University Health Science Center Associate Research Scientist
2013- 현재 Univ. Cincinnati, College of Medicine, Dept. of Environmental Health Assistant Professor
연사분을 초청하여 제 18차 정기세미나를 개최하오니 많은 참석 부탁드리겠습니다.