title: pp32r1 controls the decay of the RNA-binding protein HuR.
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.
authors.affiliation: Department of Oral Pathology and Biology, Hokkaido University Graduate School of Dental Medicine, Sapporo 060-8586, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Imamachi
authors.affiliation: Department of Oral Pathology and Biology, Hokkaido University Graduate School of Dental Medicine, Sapporo 060-8586, Japan.
authors.forename: Fumihiro
authors.initials: F
authors.lastname: Higashino
authors.affiliation: Department of Oral Pathology and Biology, Hokkaido University Graduate School of Dental Medicine, Sapporo 060-8586, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Kitamura
authors.affiliation: Department of Oral and Maxillofacial Surgery, Hokkaido University Graduate School of Dental Medicine, Sapporo 060-8586, Japan.
authors.forename: Wataru
authors.initials: W
authors.lastname: Kakuguchi
authors.affiliation: Department of Oral Pathology and Biology, Hokkaido University Graduate School of Dental Medicine, Sapporo 060-8586, Japan.
authors.forename: Aya
authors.initials: A
authors.lastname: Yanagawa-Matsuda
authors.affiliation: Department of Oral Diagnosis and Medicine, Hokkaido University Graduate School of Dental Medicine, Sapporo 060-8586, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Ishikawa
authors.affiliation: Department of Oral Diagnosis and Medicine, Hokkaido University Graduate School of Dental Medicine, Sapporo 060-8586, Japan.
authors.forename: Yoshimasa
authors.initials: Y
authors.lastname: Kitagawa
authors.affiliation: Department of Oral and Maxillofacial Surgery, Hokkaido University Graduate School of Dental Medicine, Sapporo 060-8586, Japan.
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Totsuka
authors.affiliation: Department of Oral Pathology and Biology, Hokkaido University Graduate School of Dental Medicine, Sapporo 060-8586, Japan.
authors.forename: Masanobu
authors.initials: M
authors.lastname: Shindoh
mesh_terms: D053148:Caspase 3 / Q000378:metabolism; D051959:ELAV Proteins / Q000378:metabolism*; D015870:Gene Expression; D057809:HEK293 Cells; D006801:Humans; D009687:Nuclear Proteins / Q000502:physiology*; D010750:Phosphoproteins / Q000502:physiology*; D011485:Protein Binding; D021381:Protein Transport; D059748:Proteolysis; D013312:Stress, Physiological
chemical_list: C489949:ANP32C protein, human; D051959:ELAV Proteins; D009687:Nuclear Proteins; D010750:Phosphoproteins; C505407:CASP3 protein, human; D053148:Caspase 3