The role of human prostatic acid phosphatase (PAcP, P15309|PPAP_HUMAN) in prostate cancer was investigated using a new proteomic tool termed signal sequence swapping (replacement of domains from the native cleaved amino terminal signal sequence of secretory/membrane proteins with corresponding regions of functionally distinct signal sequence subtypes). This manipulation preferentially redirects proteins to different pathways of biogenesis at the endoplasmic reticulum, magnifying normally difficult to detect subsets of the protein of interest. For PAcP this technique reveals three forms identical in amino acid sequence but profoundly different in physiological functions, subcellular location, and biochemical properties. These three forms of PAcP can also occur with the wild-type PAcP signal sequence. Clinical specimens from patients with prostate cancer demonstrate that one form, termed PLPAcP, correlates with early prostate cancer. These findings confirm the analytical power of this method, implicate PLPAcP in prostate cancer pathogenesis, and suggest novel anticancer therapeutic strategies.
Research Article|
October 04 2021
Multifunctionality of Prostatic Acid Phosphatase in Prostate Cancer Pathogenesis
Evgenia Alpert;
Evgenia Alpert
Bioconformatics laboratory of the California Pacific Medical Center (CPMC) Research Institute, Ramat-Gan, California, United States
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Armin Akhavan;
Armin Akhavan
Bioconformatics Laboratory of the California Pacific Medical Center (CPMC) Research Institute, San Francisco, California, United States
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Arie Gruzman;
Bioconformatics Laboratory of the California Pacific Medical Center (CPMC) Research Institute, San Francisco, California, United States
* Corresponding Author; email: gruzmaa@biu.ac.il
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William J Hansen;
William J Hansen
Prosetta Corporation, San Francisco, California, United States
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Joshua Lehrer- Graiwer;
Joshua Lehrer- Graiwer
Bioconformatics Laboratory of the California Pacific Medical Center (CPMC) Research Institute, San Francisco, California, United States
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Steven C Hall;
Steven C Hall
UCSF, San Francisco, California, United States
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Eric Johansen;
Eric Johansen
UCSF, San Francisco, California, United States
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Sean McAllister;
Sean McAllister
Cancer Laboratory of the California Pacific Medical Center (CPMC) Research Institute, San Francisco, California, United States
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Mittul Gulati;
Mittul Gulati
UCSF, San Francisco, California, United States
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Ming-Fong Lin;
Ming-Fong Lin
University of Nebraska Medical Center, Omaha, Nebraska, United States
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Vishwanath R Lingappa
Vishwanath R Lingappa
Bioconformatics Laboratory of the California Pacific Medical Center (CPMC) Research Institute, San Francisco, California, United States
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Publisher: Portland Press Ltd
Received:
July 14 2021
Revision Received:
September 18 2021
Accepted:
October 04 2021
Online ISSN: 1573-4935
Print ISSN: 0144-8463
Copyright 2021 The Author(s)
2021
This is an Accepted Manuscript; not the final Version of Record. You are encouraged to use the final Version of Record that, when published, will replace this manuscript and be freely available under a Creative Commons licence.
Biosci Rep (2021) BSR20211646.
Article history
Received:
July 14 2021
Revision Received:
September 18 2021
Accepted:
October 04 2021
Citation
Evgenia Alpert, Armin Akhavan, Arie Gruzman, William J Hansen, Joshua Lehrer- Graiwer, Steven C Hall, Eric Johansen, Sean McAllister, Mittul Gulati, Ming-Fong Lin, Vishwanath R Lingappa; Multifunctionality of Prostatic Acid Phosphatase in Prostate Cancer Pathogenesis. Biosci Rep 2021; BSR20211646. doi: https://doi.org/10.1042/BCJ20200944
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