Anti-apoptotic effect by the suppression of IRF1 as a downstream of Wnt/β-catenin signaling in colorectal cancer cells.


Journal

Oncogene
ISSN: 1476-5594
Titre abrégé: Oncogene
Pays: England
ID NLM: 8711562

Informations de publication

Date de publication:
08 2019
Historique:
received: 19 05 2018
accepted: 16 04 2019
revised: 27 02 2019
pubmed: 12 7 2019
medline: 29 1 2020
entrez: 12 7 2019
Statut: ppublish

Résumé

Impaired Wnt signaling pathway plays a crucial role in the development of colorectal cancer through activation of the β-catenin/TCF7L2 complex. Although genes upregulated by Wnt/β-catenin signaling have been intensively studied, the roles of downregulated genes are poorly understood. Previously, we reported that interferon-induced proteins with tetratricopeptide repeats 2 (IFIT2) was downregulated by the Wnt/β-catenin signaling, and that the suppressed expression of IFIT2 conferred antiapoptotic property to colorectal cancer (CRC) cells. However, the mechanisms underlying how Wnt/β-catenin signaling regulates IFIT2 remain to be elucidated. In this study, we have uncovered that the expression of IFIT2 is induced by IRF1, which is negatively regulated by the Wnt/β-catenin signaling. In addition, we found that downregulation of IRF1 is mediated by its degradation through the ubiquitination-proteasome pathway, and that decreased activity of a deubiquitinase complex containing USP1 and UAF1 is involved in the degradation of IRF1 by Wnt/β-catenin signaling. These data should provide better understanding of the Wnt signaling pathway and human carcinogenesis.

Identifiants

pubmed: 31292489
doi: 10.1038/s41388-019-0856-9
pii: 10.1038/s41388-019-0856-9
doi:

Substances chimiques

IRF1 protein, human 0
Interferon Regulatory Factor-1 0
Nuclear Proteins 0
USP1 associated factor 1, human 0
beta Catenin 0
USP1 protein, human EC 3.4.19.12
Ubiquitin-Specific Proteases EC 3.4.19.12

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

6051-6064

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Auteurs

Tomoyuki Ohsugi (T)

Division of Clinical Genome Research, Advanced Clinical Research Center, Institute of Medical Science, the University of Tokyo, Tokyo, 108-8639, Japan.

Kiyoshi Yamaguchi (K)

Division of Clinical Genome Research, Advanced Clinical Research Center, Institute of Medical Science, the University of Tokyo, Tokyo, 108-8639, Japan.

Chi Zhu (C)

Division of Clinical Genome Research, Advanced Clinical Research Center, Institute of Medical Science, the University of Tokyo, Tokyo, 108-8639, Japan.

Tsuneo Ikenoue (T)

Division of Clinical Genome Research, Advanced Clinical Research Center, Institute of Medical Science, the University of Tokyo, Tokyo, 108-8639, Japan.

Kiyoko Takane (K)

Division of Clinical Genome Research, Advanced Clinical Research Center, Institute of Medical Science, the University of Tokyo, Tokyo, 108-8639, Japan.

Masaru Shinozaki (M)

Department of Surgery, IMSUT Hospital, Institute of Medical Science, the University of Tokyo, Tokyo, 108-8639, Japan.

Giichiro Tsurita (G)

Department of Surgery, IMSUT Hospital, Institute of Medical Science, the University of Tokyo, Tokyo, 108-8639, Japan.

Hideaki Yano (H)

Department of Surgery, Center Hospital of the National Center for Global Health and Medicine, Tokyo, 162-8655, Japan.

Yoichi Furukawa (Y)

Division of Clinical Genome Research, Advanced Clinical Research Center, Institute of Medical Science, the University of Tokyo, Tokyo, 108-8639, Japan. furukawa@ims.u-tokyo.ac.jp.

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Classifications MeSH