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USP32 is an active, membrane-bound ubiquitin protease overexpressed in breast cancers

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Abstract

USP32, on chromosomal band 17q23.1-17q23.2, is a highly conserved but uncharacterized gene that gave rise during evolution to a well-known hominoid-specific proto-oncogene, USP6. We investigated the expression profile of USP32 in human tissues and examined its functions to gain insight into this novel member of the well-conserved ubiquitination system. We detected ubiquitous USP32 expression across tissues and confirmed the predicted deubiquitination function owing to the presence of conserved peptidase signature aspargine, cysteine, histidine, and aspartic acid domains of ubiquitin-specific proteases. A Golgi localization of GFP-fused USP32 was detected by fluorescent protection assay and BODIPY-TR staining. In addition, stable silencing of USP32 caused a significant decrease in the proliferation and migration rate of cells. Based on these and the fact that USP32 maps to 17q23, which is commonly amplified in breast cancers, we analyzed USP32 expression in breast cancer cells. We detected high expression of USP32 in 50% (9 of 18) of breast cancer cell lines and 22% (9 of 41) of primary breast tumors compared to mammary epithelial cells. In summary, we report the preliminary characterization of this novel deubiquitinating enzyme on 17q23 and demonstrate its functional role in the ubiquitin system and its potential involvement in tumorigenesis.

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Acknowledgments

This project was funded by the Scientific and Technological Research Council of Turkey (TUBITAK) (104S241, 108S408) and METU internal funds. A. Sapmaz is funded by OYP (YYU, Van). Contributions by J. Keller and E. Petty were supported by NIH-NCI RO1 CA72877-01A1. We thank Drs. C. Yakicier and U. Tazebay for sharing resources, T. Acun for technical help, Drs. C. Ozen, P. Ballar, and C. Son for guidance with microscopy, Dr. M. Gürsel for flow cytometry, Dr. M. Hochstrasser for constructs/protocols, and Dr. V. Seyrantepe for pEGFP vectors.

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Authors and Affiliations

  1. Department of Biological Sciences, Inonu Bulvarı, M.E.T.U, 06531, Ankara, Turkey

    Shiva Akhavantabasi, Hesna B. Akman, Aysegul Sapmaz & Ayse E. Erson

  2. Department of Internal Medicine and Human Genetics, University of Michigan, 5220 MSRB III, 1150 West Medical Center Drive, Ann Arbor, MI, 48109-0640, USA

    Jennifer Keller & Elizabeth M. Petty

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  1. Shiva Akhavantabasi
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  2. Hesna B. Akman
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  3. Aysegul Sapmaz
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  4. Jennifer Keller
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  5. Elizabeth M. Petty
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  6. Ayse E. Erson
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Correspondence to Ayse E. Erson.

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S. Akhavantabasi, H. B. Akman, and A Sapmaz contributed equally to this work.

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Akhavantabasi, S., Akman, H.B., Sapmaz, A. et al. USP32 is an active, membrane-bound ubiquitin protease overexpressed in breast cancers. Mamm Genome 21, 388–397 (2010). https://doi.org/10.1007/s00335-010-9268-4

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  • DOI: https://doi.org/10.1007/s00335-010-9268-4

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