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제120회 대한화학회 학술발표회, 총회 및 기기전시회 안내 Regulation of cellular proteasomal activity and autophagic flux via USP14 deubiquitinase

등록일
2017년 9월 6일 17시 43분 22초
접수번호
2513
발표코드
BIO.P-293 이곳을 클릭하시면 발표코드에 대한 설명을 보실 수 있습니다.
발표시간
10월 19일 (목요일) 11:00~12:30
발표형식
포스터
발표분야
Life Chemistry
저자 및
공동저자
Kim Eunkyoung, Seoyoung Park1, Min Jae Lee*
College of Medicine, Biochemistry, Seoul National University, Korea
11Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine, Korea
Two major intracellular pathways regulating protein degradation are the ubiquitin-proteasome system (UPS) and the autophagy-lysosome system (autophagy). Several biochemical mechanisms underlying the possible complementary relation between two of them have been suggested, however, little is known about the effect of enhanced proteasome activity on autophagic flux and its proteostatic consequences. Here, we found that activation of the proteasome through chemical and genetic inhibition of USP14, a proteasome-associated deubiquitinating enzyme, results in downregulation of autophagic flux in the cell. This autophagic impairment resulted mainly from delayed autophagosome-lysosome fusion and from abnormal turnover of UVRAG, a tumor suppressor and autophagic maturation regulator. Moreover, while proteasome activation through USP14 inhibition facilitated the clearance of a proteotoxic protein Tau and reduced the amount of its oligomeric forms, the same conditions increased formation of inclusion bodies from non-proteasomal substrates such as huntingtin with long polyglutamine repeats. Taken together, our results suggested that USP14 may function as a common denominator in the compensatory negative feedback relation between the two major proteolytic processes in the cell. This biochemical connection may underline a more precise therapeutic strategy for various pathological conditions due to impaired UPS or autophagy.

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