TY - JOUR
T1 - Multifunctionality of prostatic acid phosphatase in prostate cancer pathogenesis
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).
PY - 2021/10
Y1 - 2021/10
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85118764533&partnerID=8YFLogxK
U2 - 10.1042/BSR20211646
DO - 10.1042/BSR20211646
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C2 - 34605872
SN - 0144-8463
VL - 41
JO - Bioscience Reports
JF - Bioscience Reports
IS - 10
M1 - BSR20211646
ER -
