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The TRIM-FLMN protein TRIM45 directly interacts with RACK1 and negatively regulates PKC-mediated signaling pathway

Oncogene volume 34, pages 1280–1291 (2015)Cite this article

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Abstract

The receptor for activated C-kinase (RACK1), a scaffolding protein that participates in the protein kinase C (PKC) signaling pathway, has an important role in shuttling active PKCs to its substrate. Indeed, recent studies have revealed that RACK1 has an important role in tumorigenesis and that enhancement of the feed-forward mechanism of the c-Jun N-terminal kinase (JNK)–Jun pathway via RACK1 is associated with constitutive activation of MEK (MAPK-ERK kinase)–ERK (extracellular signal-regulated kinase) signaling in human melanoma cells. Taken together, RACK1 additionally has a very important role in the mitogen-activated protein kinase (MAPK) signaling pathway. Here, we show that one of the tripartite motif-containing (TRIM) family ubiquitin ligases, TRIM45, is a novel RACK1-interacting protein and downregulates MAPK signal transduction. Importantly, the expression of TRIM45 is induced when growth-promoting extracellular stimuli activate the MAPK signaling pathway, resulting in attenuation of activation of the MAPK pathway. These findings suggest that TRIM45 functions as a member of the negative feedback loop of the MAPK pathway.

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Acknowledgements

We thank Dr Toshio Kitamura (Tokyo University) for the plasmid and cell lines. This work was supported in part by a research grant from Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology in Japan, Japan Foundation for Applied Enzymology, and Children’s Cancer Association of Japan.

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Authors and Affiliations

  1. Department of Pediatrics, Hokkaido University Graduate School of Medicine, Sapporo, Japan

    T Sato, A Iguchi & T Ariga

  2. Department of Biochemistry, Hokkaido University Graduate School of Medicine, Sapporo, Japan

    T Sato, H Takahashi & S Hatakeyama

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  1. T Sato
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Correspondence to T Sato.

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Sato, T., Takahashi, H., Hatakeyama, S. et al. The TRIM-FLMN protein TRIM45 directly interacts with RACK1 and negatively regulates PKC-mediated signaling pathway. Oncogene 34, 1280–1291 (2015). https://doi.org/10.1038/onc.2014.68

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