제 250회 NEBS Monthly meeting 개최를 다음과 같이 알려드립니다.
일시: 2016년 10월 27일 (목요일) 오후 6시 30분
(7시 이후 엘레베이터 이용이 제한되니 가급적 7시 이전에 오시길 부탁드리며, 7시 이후의 경우 Security guard에게 미팅 참석 여부를 확인 후 엘리베이터 이용을 부탁해 주세요.)
New Research Building, 10th floor conference room
77 Ave Louis Pasteur, Boston, MA 02115
6:20 - 7:00 저녁식사
7:00 - 7:10 공지사항
7:10 – 7:50 학술 세미나 1 -
“U2AF35(S34F) Promotes Transformation by Directing Aberrant ATG7 Pre-mRNA 30 End Formation”
By Sungmi Park, Ph.D (UMass Medical School)
7:50 - 8:30 학술 세미나 2 –
“Building a tension at the cell-cell adhesion: A nanoscale view”
By Wangsun Choi, Ph.D (Brigham and Women’s Hospital)
- 11:00 뒷풀이 (Longwood Grill)
미팅 참석시 주차는 375 Longwood garage (http://www.masco.org/directions/375-longwood-garage)를 이용해주시기 바랍니다. 당일날 참석인원 확인용지에 주소를 기입해주시면 주차 지원비 7불을 check 으로 발송해 드리겠습니다 (미팅에 오실때 카풀을 하시는 분들을우선적으로 지원해드리기로 되어 있습니다).
회원 여러분들의 많은 참여 부탁드립니다.
세미나 초록은 아래를 참고해 주시길 바랍니다.
Title: U2AF35(S34F) Promotes Transformation by Directing Aberrant ATG7 Pre-mRNA 30 End Formation
Recurrent mutations in the splicing factor U2AF35 are found in several cancers and myelodysplastic syndrome (MDS). How oncogenic U2AF35 mutants promote transformation remains to be determined. Here we derive cell lines transformed by the oncogenic U2AF35(S34F) mutant and identify aberrantly processed pre-mRNAs by deep sequencing. We find that in U2AF35(S34F)-transformed cells the autophagy-related factor 7 (Atg7) pre-mRNA is
abnormally processed, which unexpectedly is not due to altered splicing but rather selection of a distal cleavage and polyadenylation (CP) site. This longer Atg7 mRNA is translated inefficiently, leading to decreased ATG7 levels and an autophagy defect that predisposes cells to secondary mutations, resulting in transformation. MDS and acute myeloid leukemia patient samples harboring U2AF35(S34F) have a similar increased use of the ATG7 distal CP site, and previous studies have shown that mice with hematopoietic cells lacking Atg7 develop an MDS-like syndrome. Collectively, our results reveal a basis for U2AF35(S34F) oncogenic activity.
Title: Building a tension at the cell-cell adhesion: A nanoscale view
Morphogenesis and epithelial homeostasis require dynamic coordination between cell-cell adhesion and cytoskeletal tension at cell-cell junctions. In the past decade, it has become increasingly clear that the textbook view of the cell-cell zonula adherens (ZA), as a static ring of transmembrane cadherins linked to an underlying ring of actin and myosin via catenins, is misleading. Here we addressed two key questions in the field: how do cells maintain epithelial integrity under tension and how are cell junctions remodeled in response to tension to ensure this. We used super-resolution microscopy, tension-sensing antibodies, and nanoscale laser ablation to define the architecture of junctions and the cytoskeleton under tension in molecular detail, and to determine how changes in individual cells alter the architecture and properties of the entire epithelial sheet. When cells undergo an increase in contractility, the architecture of actin and myosin at the ZA remodels into a contractile array at the bi-cellular contacts with the actin cables anchored end on into cadherin complexes at tricellular junctions. We found that Rho-dependent kinase (ROCK) and Shroom3 proteins promotes the increase in contractility whereas ZO family proteins normally suppress actomyosin contractility at the ZA. We also found a striking role for afadin which regulates the uniform distribution of actomyosin units at cell-cell contacts in response to increased tension. Our findings refine the roles of key scaffolding proteins in organizing and anchoring junctions in epithelia.