Multifunctionality of prostatic acid phosphatase in prostate cancer pathogenesis

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

doi:10.1042/BSR20211646

Multifunctionality of prostatic acid phosphatase in prostate cancer pathogenesis

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

California Pacific Medical Center
PROSETTA CORPORATION
University of California at San Francisco
University of Nebraska Medical Center

Research output: Contribution to journal › Article › peer-review

14 Scopus citations

Abstract

The role of human prostatic acid phosphatase (PAcP, P15309|PPAP HUMAN) in prostate cancer was investigated using a new proteomics 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 (ER), 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 wildtype 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.

Original language	English
Article number	BSR20211646
Journal	Bioscience Reports
Volume	41
Issue number	10
Early online date	4 Oct 2021
DOIs	https://doi.org/10.1042/BSR20211646
State	Published - Oct 2021
Externally published	Yes

Bibliographical note

Publisher Copyright:
© 2021 The Author(s). This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY).

Funding

This work supported by the NIH (to Ming-Fong Lin and Vishwanath R. Lingappa); the CPMC Research Institute; and the Prosetta Corporation of which Vishwanath R. Lingappa is a founder and Chief Technology Officer.

Funders
CPMC Research Institute
Chief Technology Officer
National Institutes of Health

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

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10.1042/BSR20211646

Cite this

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title = "Multifunctionality of prostatic acid phosphatase in prostate cancer pathogenesis",

abstract = "The role of human prostatic acid phosphatase (PAcP, P15309|PPAP HUMAN) in prostate cancer was investigated using a new proteomics 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 (ER), 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 wildtype 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.",

author = "Evgenia Alpert and Armin Akhavan and Arie Gruzman and Hansen, \{William J.\} and Joshua Lehrer-Graiwer and Hall, \{Steven C.\} and Eric Johansen and Sean McAllister and Mittul Gulati and Lin, \{Ming Fong\} and Lingappa, \{Vishwanath R.\}",

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doi = "10.1042/BSR20211646",

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AU - Alpert, Evgenia

AU - Akhavan, Armin

AU - Gruzman, Arie

AU - Hansen, William J.

AU - Lehrer-Graiwer, Joshua

AU - Hall, Steven C.

AU - Johansen, Eric

AU - McAllister, Sean

AU - Gulati, Mittul

AU - Lin, Ming Fong

AU - Lingappa, Vishwanath R.

N1 - Publisher Copyright: © 2021 The Author(s). This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY).

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Multifunctionality of prostatic acid phosphatase in prostate cancer pathogenesis

Abstract

Bibliographical note

Funding

UN SDGs

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