pp32r1 controls the decay of the RNA-binding protein HuR

Imamachi,Kenji; Higashino,Fumihiro; Kitamura,Tetsuya; Kakuguchi,Wataru; Yanagawa-Matsuda,Aya; Ishikawa,Makoto; Kitagawa,Yoshimasa; Totsuka,Yasunori; Shindoh,Masanobu

doi:10.3892/or.2013.2956

pp32r1 controls the decay of the RNA-binding protein HuR

Authors:
- Kenji Imamachi
- Fumihiro Higashino
- Tetsuya Kitamura
- Wataru Kakuguchi
- Aya Yanagawa-Matsuda
- Makoto Ishikawa
- Yoshimasa Kitagawa
- Yasunori Totsuka
- Masanobu Shindoh
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Affiliations: Department of Oral Pathology and Biology, Hokkaido University Graduate School of Dental Medicine, Sapporo 060-8586, Japan, Department of Oral and Maxillofacial Surgery, Hokkaido University Graduate School of Dental Medicine, Sapporo 060-8586, Japan, Department of Oral Diagnosis and Medicine, Hokkaido University Graduate School of Dental Medicine, Sapporo 060-8586, Japan
Published online on: December 31, 2013 https://doi.org/10.3892/or.2013.2956
Pages: 1103-1108

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Abstract

pp32 is a tumor suppressor and is one of the associated proteins of the RNA-binding protein HuR. The pp32-HuR complex is exported to the cytoplasm of cells under stress conditions, and HuR is degraded by caspases in the cytoplasm. In the present study, we examined the role of pp32r1, a member of the pp32 family that has oncogenic properties, in the decay of HuR. pp32r1 was found to be abundantly expressed in cancer cells, and overexpression of pp32r1 induced colony formation in soft-agar. pp32r1 was expressed in both the nucleus and cytoplasm, whereas pp32 was predominantly localized in the nucleus. Even with lethal stress such as staurosporine (STS), HuR in the cytoplasm was never downregulated, and caspase-3 activity was inhibited when cells expressed pp32r1. pp32r1 bound to HuR without interacting with pp32. In cancer cells, HuR survived in the cytoplasm of cells overexpressing pp32r1, although HuR was not expressed in the cytoplasm of pp32-expressing cells, similar to lethal stress conditions. Taken together, these results indicate that pp32r1 binds to HuR to avoid the caspase-mediated decay of HuR in the cytoplasm of cells. We suggest that this function contributes to the oncogenic activity of pp32r1.

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