충북대학교 종양연구소에서 다음과 같이 초청세미나를 개최하오니 많은 참여 부탁드립니다.
- 다 음 -
1. 연 자 : 류 춘 제 교수 (세종대학교)
2. 일 시 : 2016년 05월 03일 (화) 오후 5시
3. 연 제 : Cell surface-expressed HNRPUL1/E1B-AP5 regulates proliferation of human
pluripotent stem cell and cancer cell via Wnt/GSK3β/β-catenin signaling.
4. 장 소 : 종양연구소 세미나실 104호
5. 발 표 내 용
Heterogeneous nuclear ribonucleoprotein U like 1/Adenovirus early region 1B-associated protein 5 (HNRPUL1/E1B-AP5) is involved in multifunctional RNA processing and DNA damage repair. Previously, we generated murine monoclonal antibodies (MAbs) specific to surface antigens of undifferentiated human pluripotent stem cells (hPSCs) and showed that 57-C11, one of the MAbs, recognized HNRPUL1 on the surface of hPSCs. Interestingly, cell surface expression of HNRPUL1 was restricted to hPSCs and a few cancer cell lines such as A375 and U2OS, although HNRPUL1 has been known to be ubiquitously expressed in the cytoplasm and nucleus in various cells. To understand the biological function of HNRPUL1 on the surface, in this study, we performed siRNA-mediated knockdown of HNRPUL1 in hPSCs and some cancer cell lines. HNRPUL1 knockdown inhibited cell proliferation and differentiation without inducing cell death and promoted cell cycle arrest in G0/G1 phase in hPSCs. Similar effects were observed in shRNA-mediated knockdown of HNRPUL1 in hPSCs. HNRPUL1 knockdown inhibited cell proliferation in cancer cell lines as well but did not induce specific cell cycle arrest, suggesting that HNRPUL1 plays additional roles in G1/S transition phase in hPSCs. Interestingly, HNRPUL1 knockdown induced cell death in HeLa cells where cell surface expression of HNRPUL1 was not observed. The human phospho-MAPK antibody array showed that PI3K/AKT, MEK/ERK, and Wnt/GSK3β/β-catenin signaling were downregulated in HNRPUL1 knockdown hPSCs. To further investigate the functional role of HNRPUL1 on the cell surface, hPSCs and A375 cells were treated with 57-C11 and/or anti-E1B-AP5 antibodies. Antibody treatment suppressed cell proliferation without the alteration of cell cycle and death and reduced only Wnt/GSK3β/β-catenin signaling in both hPSCs and A375 cells, suggesting that cell surface-expressed HNRPUL1 regulates cell proliferation via Wnt/GSK3β/β-catenin signaling. These findings provide for the first time mechanistic insight into how HNRPUL1 regulates hPSC and cancer cell proliferation on the surface.