The roles of ubiquitination in extrinsic cell death pathways and its implications for therapeutics

Jinho Seo, Min Wook Kim, Kwang Hee Bae, Sang Chul Lee, Jaewhan Song, Eun Woo Lee

Research output: Contribution to journalReview articlepeer-review

26 Citations (Scopus)


Regulation of cell survival and death, including apoptosis and necroptosis, is important for normal development and tissue homeostasis, and disruption of these processes can cause cancer, inflammatory diseases, and degenerative diseases. Ubiquitination is a cellular process that induces proteasomal degradation by covalently attaching ubiquitin to the substrate protein. In addition to proteolytic ubiquitination, nonproteolytic ubiquitination, such as M1-linked and K63-linked ubiquitination, has been shown to be important in recent studies, which have demonstrated its function in cell signaling pathways that regulate inflammation and cell death pathways. In this review, we summarize the TRAIL- and TNF-induced death receptor signaling pathways along with recent advances in this field and illustrate how different types of ubiquitination control cell death and survival. In particular, we provide an overview of the different types of ubiquitination, target residues, and modifying enzymes, including E3 ligases and deubiquitinating enzymes. Given the relevance of these regulatory pathways in human disease, we hope that a better understanding of the regulatory mechanisms of cell death pathways will provide insights into and therapeutic strategies for related diseases.

Original languageEnglish
Pages (from-to)21-40
Number of pages20
JournalBiochemical Pharmacology
Publication statusPublished - 2019 Apr

Bibliographical note

Funding Information:
This study was supported by grants from the Korea Research Institute of Bioscience and Biotechnology (KRIBB) and by grants from the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT and Future Planning ( 2013M3A9A7046301 , 2015M3A9D7029882 , 2015R1A3A2066581 , 2017R1A6A3A11035262 , and 2017M3A9G5083321 ).

Publisher Copyright:
© 2018 Elsevier Inc.

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Pharmacology


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