[대학원 생명과학과 세미나 안내] 
 
연사 : 김경미 박사(National Institute of Health)

연제 : Characterization of cell-surface senescence marker protein DPP4
  
일시 : 2017년 2월 23일 (목) 오후 4시

장소 : 하나과학관 A동 207호

초청교수 : 김윤기 교수

Abstract

In response to a wide range of damaging conditions, cells can adopt a senescent phenotype, characterized by indefinite growth arrest and expression of distinct sets of RNAs and proteins.  Given the impact of senescence on many disease processes, there is great interest in identifying senescent markers that can be exploited in therapeutic interventions. We recently employed cell fractionation and mass spectrometry experiments to identify cell surface proteins selectively expressed in senescent cells.  Using proliferating and senescent WI-38 human fibroblasts, we identified 118 proteins present both in the membrane fraction and in the cell surface; among them, DPP4 (dipeptidyl-peptidase 4) was found expressed at much higher levels in both senescent cells. DPP4 is known to function as an enzyme involved in glucose metabolism.  First, we tested if DPP4 was due to increased levels of the corresponding mRNAs.  By reverse transcription (RT) and quantitative (q)PCR analysis, we found that relative to proliferating cells, extremely high levels of DPP4 mRNA and this rise likely explained the high levels of DPP4 protein in senescent cells. Initial molecular characterization revealed that the rise in DPP4 was due to a robust increase in DPP4 mRNA transcription.  Given that DPP4 are abundant on the surface of senescent cells, we hypothesize that senescent cells might be selectively eliminated via targeting this specific membrane protein.  To test this hypothesis, we tested that DPP4 is accessible to the outside of the cell and then we will begin the exciting development of antibody-dependent cell mediated cytotoxicity (ADCC) to target and eliminate senescent cells selectively by targeting DPP4. Given their localization on the cell surface, we propose that DPP4 is promising therapeutic targets in interventions aimed selectively at senescent cells.