Covalent ISG15 conjugation to CHIP promotes its ubiquitin E3 ligase activity and inhibits lung cancer cell growth in response to type I interferon
- Title
- Covalent ISG15 conjugation to CHIP promotes its ubiquitin E3 ligase activity and inhibits lung cancer cell growth in response to type I interferon
- Author
- 윤채옥
- Keywords
- HSC70-INTERACTING PROTEIN CHIP; C-MYC EXPRESSION; MEDIATED DEGRADATION; IDENTIFICATION; ARREST; ACTIVATION; APOPTOSIS; CYTOKINE; TERMINUS; TARGET
- Issue Date
- 2018-01
- Publisher
- NATURE PUBLISHING GROUP
- Citation
- CELL DEATH & DISEASE, v. 9, Article no. 97
- Abstract
- The carboxyl terminus of Hsp70-interacting protein (CHIP) acts as a ubiquitin E3 ligase and a link between the chaperones Hsp70/90 and the proteasome system, playing a vital role in maintaining protein homeostasis. CHIP regulates a number of proteins involved in a myriad of physiological and pathological processes, but the underlying mechanism of action via posttranslational modification has not been extensively explored. In this study, we investigated a novel modulatory mode of CHIP and its effect on CHIP enzymatic activity. ISG15, an ubiquitin-like modifier, is induced by type I interferon (IFN) stimulation and can be conjugated to target proteins (ISGylation). Here we demonstrated that CHIP may be a novel target of ISGylation in HEK293 cells stimulated with type I IFN. We also found that Lys143/144/145 and Lys287 residues in CHIP are important for and target residues of ISGylation. Moreover, ISGylation promotes the E3 ubiquitin ligase activity of CHIP, subsequently causing a decrease in levels of oncogenic c-Myc, one of its many ubiquitination targets, in A549 lung cancer cells and inhibiting A549 cell and tumor growth. In conclusion, the present study demonstrates that covalent ISG15 conjugation produces a novel CHIP regulatory mode that enhances the tumor-suppressive activity of CHIP, thereby contributing to the antitumor effect of type I IFN.
- URI
- https://www.nature.com/articles/s41419-017-0138-9https://repository.hanyang.ac.kr/handle/20.500.11754/116984
- ISSN
- 2041-4889
- DOI
- 10.1038/s41419-017-0138-9
- Appears in Collections:
- COLLEGE OF ENGINEERING[S](공과대학) > BIOENGINEERING(생명공학과) > Articles
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