TRIM48 Promotes ASK1 Activation and Cell Death through Ubiquitination-Dependent Degradation of the ASK1-Negative Regulator PRMT1
| Autor: | Takuya Noguchi, Tomohisa Hatta, Atsushi Matsuzawa, Tsuyoshi Udagawa, Junken Aoki, Tohru Natsume, Kuniyuki Kano, Hidenori Ichijo, Keita Nagaoka, Isao Naguro, Toshifumi Inada, Yuki Kudoh, Yusuke Hirata, Kazumi Katagiri, Tohru Morishita |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Protein-Arginine N-Methyltransferases tumor Programmed cell death PRMT1 Regulator Biology MAP Kinase Kinase Kinase 5 General Biochemistry Genetics and Molecular Biology Cell Line Tripartite Motif Proteins 03 medical and health sciences 0302 clinical medicine Ubiquitin ubiquitin Humans oxidative stress cancer ASK1 lcsh:QH301-705.5 Cell Death Kinase Ubiquitination apoptosis MAPK Cell biology Repressor Proteins Crosstalk (biology) 030104 developmental biology lcsh:Biology (General) Apoptosis 030220 oncology & carcinogenesis Cancer research biology.protein TRIM48 Thioredoxin |
| Zdroj: | Cell Reports, Vol 21, Iss 9, Pp 2447-2457 (2017) |
| ISSN: | 2211-1247 |
| DOI: | 10.1016/j.celrep.2017.11.007 |
| Popis: | Summary Apoptosis signal-regulating kinase 1 (ASK1) is an oxidative stress-responsive kinase that is regulated by various interacting molecules and post-translational modifications. However, how these molecules and modifications cooperatively regulate ASK1 activity remains largely unknown. Here, we showed that tripartite motif 48 (TRIM48) orchestrates the regulation of oxidative stress-induced ASK1 activation. A pull-down screen identified a TRIM48-interacting partner, protein arginine methyltransferase 1 (PRMT1), which negatively regulates ASK1 activation by enhancing its interaction with thioredoxin (Trx), another ASK1-negative regulator. TRIM48 facilitates ASK1 activation by promoting K48-linked polyubiquitination and degradation of PRMT1. TRIM48 knockdown suppressed oxidative stress-induced ASK1 activation and cell death, whereas forced expression promoted cancer cell death in mouse xenograft model. These results indicate that TRIM48 facilitates oxidative stress-induced ASK1 activation and cell death through ubiquitination-dependent degradation of PRMT1. This study provides a cell death mechanism fine-tuned by the crosstalk between enzymes that engage various types of post-translational modifications. |
| Databáze: | OpenAIRE |
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