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Interaction and colocalization of PGP9.5 with JAB1 and p27Kip1

Oncogene volume 21, pages 3003–3010 (2002)Cite this article

Abstract

PGP9.5 (UCH-L1) is a member of the ubiquitin C-terminal hydrolase (UCH) family of proteins that is expressed in neuronal tissues. Our previous studies have shown that PGP9.5 was highly expressed in primary lung cancers and lung cancer cell lines. Additionally, the frequency of PGP9.5 over expression increases with tumor stage, indicating that PGP9.5 may play a role in lung cancer tumorigenesis. We used the yeast two-hybrid system to identify proteins that interact with PGP9.5. We show that PGP9.5 interacts with at least three proteins, one of which is JAB1, a Jun activation domain binding protein that can bind to p27Kip1 and is involved in the cytoplasmic transportation of p27Kip1 for its degradation. We also show that PGP9.5 is associated with JAB1 in vitro and in vivo; and that both proteins can be a part of a heteromeric complex containing p27Kip1 in the nucleus in lung cancer cells. Furthermore, under serum-restimulation, nuclear translocation of both PGP9.5 and JAB1 coincides with a reduced level of p27Kip1 in the nucleus. In contrast, when cells are contact inhibited, both PGP9.5 and JAB1 became more perinuclear and cytoplasmic in localization while p27Kip1 was present only in the nucleus. Therefore, PGP9.5 may contribute to p27Kip1 degradation via its interaction and nuclear translocation with JAB1.

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Acknowledgements

We thank Drs Chi V Dang, Cecile Pickart, and Michael Matunis for helpful discussions during the course of this project. This work was supported in part by the NCI Lung SPORE grant CA 58184. OL Caballero is also supported by Fundação de Amparo à Pesquisa do Estado de São Paulo, Brazil (FAPESP).

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Authors and Affiliations

  1. Department of Otolaryngology-Head and Neck Surgery, Division of Head and Neck Cancer Research, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA

    Otávia L Caballero, Vicente Resto, Meera Patturajan, Ming Zhou Guo, James Engles, Robert Yochem, Edward Ratovitski, David Sidransky & Jin Jen

  2. The Laboratory of Population Genetics, Centre for Cancer Research, National Cancer Institute, Building 41, Rm D702, 41 Library Drive, Bethesda, MD 20892, Maryland, USA

    Daoud Meerzaman & Jin Jen

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  1. Otávia L Caballero
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Correspondence to Jin Jen.

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Caballero, O., Resto, V., Patturajan, M. et al. Interaction and colocalization of PGP9.5 with JAB1 and p27Kip1. Oncogene 21, 3003–3010 (2002). https://doi.org/10.1038/sj.onc.1205390

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