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김성태
김성태 (Sung Tae Kim) 저자 이메일 보기
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조회 2842  인쇄하기 주소복사 트위터 공유 페이스북 공유 
[Autophagic Punctum] The N-end rule proteolytic system in autophagy

Sung Tae Kim, Takafumi Tasaki, Adriana Zakrzewska, Young Dong Yoo, Ki Sa Sung, Su-Hyeon Kim, Hyunjoo Cha-Molstad, Joonsung Hwang, Kyoung A Kim, Bo Yeon Kim*, Yong Tae Kwon 

Sung Tae Kim
Center for Pharmacogenetics and Department of Pharmaceutical Sciences; School of Pharmacy; University of Pittsburgh; Pittsburgh, PA USA
These authors equally contributed to this work.
Takafumi Tasaki
Medical Research Institute; Kanazawa Medical University; Ishikawa, Japan
These authors equally contributed to this work.
Adriana Zakrzewska
Center for Pharmacogenetics and Department of Pharmaceutical Sciences; School of Pharmacy; University of Pittsburgh; Pittsburgh, PA USA
These authors equally contributed to this work.
Young Dong Yoo
World Class University (WCU) Program; Department of Molecular Medicine and Biopharmaceutical Sciences; Graduate School of Convergence Science and Technology and College of Medicine; Seoul National University; Seoul, Korea; Department of Biomedical Sciences; College of Medicine; Seoul National University; Seoul, Korea
Ki Sa Sung
Center for Pharmacogenetics and Department of Pharmaceutical Sciences; School of Pharmacy; University of Pittsburgh; Pittsburgh, PA USA
Su-Hyeon Kim
Center for Pharmacogenetics and Department of Pharmaceutical Sciences; School of Pharmacy; University of Pittsburgh; Pittsburgh, PA USA; World Class Institute; Korea Research Institute of Bioscience and Biotechnology; Ochang Cheongwon, Korea
Hyunjoo Cha-Molstad
World Class Institute; Korea Research Institute of Bioscience and Biotechnology; Ochang Cheongwon, Korea
Joonsung Hwang
World Class Institute; Korea Research Institute of Bioscience and Biotechnology; Ochang Cheongwon, Korea
Kyoung A Kim
World Class Institute; Korea Research Institute of Bioscience and Biotechnology; Ochang Cheongwon, Korea
Bo Yeon Kim
*Corresponding autho
World Class Institute; Korea Research Institute of Bioscience and Biotechnology; Ochang Cheongwon, Korea
Yong Tae Kwon
*Corresponding author
Center for Pharmacogenetics and Department of Pharmaceutical Sciences; School of Pharmacy; University of Pittsburgh; Pittsburgh, PA USA; World Class University (WCU) Program; Department of Molecular Medicine and Biopharmaceutical Sciences; Graduate School of Convergence Science and Technology and College of Medicine; Seoul National University; Seoul, Korea; Department of Biomedical Sciences; College of Medicine; Seoul National University; Seoul, Korea

Abstract
The N-end rule pathway is a cellular proteolytic system that utilizes specific N-terminal residues as degradation determinants, called N-degrons. N-degrons are recognized and bound by specific recognition components (N-recognins) that mediate polyubiquitination of low-abundance regulators and selective proteolysis through the proteasome. Our earlier work identified UBR4/p600 as one of the N-recognins that promotes N-degron-dependent proteasomal degradation. In this study, we show that UBR4 is associated with cellular cargoes destined to autophagic vacuoles and is degraded by the lysosome. UBR4 loss causes multiple misregulations in autophagic pathways, including an increased formation of LC3 puncta. UBR4-deficient mice die during embryogenesis primarily due to defective vascular development in the yolk sac (YS), wherein UBR4 is associated with a bulk lysosomal degradation system that absorbs maternal proteins from the YS cavity and digests them into amino acids. Our results suggest that UBR4 plays a role not only in selective proteolysis of short-lived regulators through the proteasome, but also bulk degradation through the lysosome. Here, we discuss a possible mechanism of UBR4 as a regulatory component in the delivery of cargoes destined to interact with the autophagic core machinery.

Keywords: N-recognin, UBR box, UBR4, angiogenesis, ubiquitin ligase, yolk sac

논문정보
- 형식: Autophagic Punctum
- 게재일: 2013년 07월 (BRIC 등록일 2013-07-02)
- 연구진: 국내(교신)+국외 연구진태극기
- 분야: Cell_Biology
광유전학의 과거, 현재와 미래[Neuron]
김윤석
발표: 김윤석 (Stanford University)
일자: 2020년 7월 30일 (목) 오후 02시 (한국시간)
언어: 한국어
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