Cytosolic Aryl Sulfotransferase 4A1 Interacts with the Peptidyl Prolyl Cis-Trans Isomerase Pin1

Mitchell, Deanne J. and Minchin, Rodney F. (2009) Cytosolic Aryl Sulfotransferase 4A1 Interacts with the Peptidyl Prolyl Cis-Trans Isomerase Pin1. Molecular Pharmacology, 76 2: 388-395. doi:10.1124/mol.109.055442

Author Mitchell, Deanne J.
Minchin, Rodney F.
Title Cytosolic Aryl Sulfotransferase 4A1 Interacts with the Peptidyl Prolyl Cis-Trans Isomerase Pin1
Journal name Molecular Pharmacology   Check publisher's open access policy
ISSN 0026-895X
Publication date 2009-08-01
Year available 2009
Sub-type Article (original research)
DOI 10.1124/mol.109.055442
Open Access Status Not yet assessed
Volume 76
Issue 2
Start page 388
End page 395
Total pages 8
Editor Jeffrey P Conn
Jill Filler
Place of publication United States
Publisher American Society for Pharmacology & Experimental Therapeutics
Language eng
Subject 110312 Nephrology and Urology
111601 Cell Physiology
060110 Receptors and Membrane Biology
060111 Signal Transduction
970106 Expanding Knowledge in the Biological Sciences
Abstract Sulfonation by cytosolic sulfotransferases plays an important role in the metabolism of both endogenous and exogenous compounds. Sulfotransferase 4A1 (SULT4A1) is a novel sulfotransferase found primarily in neurons in the brain. It is highly conserved between species, but no substantial enzyme activity has been identified for the protein. Consequently, little is known about the role of this enzyme in the brain. We performed a yeast two-hybrid screen of a human brain library to isolate potential SULT4A1-interacting proteins that might identify the role or regulation of the sulfotransferase in humans. The screen isolated the peptidyl-prolyl cis-trans isomerase Pin1. Its interaction with SULT4A1 was confirmed by coimmunoprecipitation studies in HeLa cells and by in vitro pull-down of expressed proteins. Moreover, Pin1 binding was dependent on phosphorylation of the SULT4A1 protein. Pin1 destabilized SULT4A1, decreasing its half-life from more than 8 h to approximately 4.5 h. This effect was dependent on the isomerase activity of Pin1 and was inhibited by okadaic acid, suggesting a role for the phosphatase PP2A. Pin1-mediated SULT4A1 degradation did not involve the proteosomes or macroautophagy, but it was inhibited by the calpain antagonists N-acetyl-Leu-Leu-Nle-CHO and Z-Val-Phe-CHO. Finally, Pin1 binding was mapped to two threonine-proline motifs (Thr(8) and Thr(11)) that are not present in any of the other human cytosolic sulfotransferases. Our findings suggest that SULT4A1 is subject to post-translational modification that alters its stability in the cell. These modifications may also be important for enzyme activity, which explains why specific substrates for SULT4A1 have not yet been identified.
Q-Index Code C1
Q-Index Status Confirmed Code

Document type: Journal Article
Sub-type: Article (original research)
Collections: 2010 Higher Education Research Data Collection
School of Biomedical Sciences Publications
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Citation counts: TR Web of Science Citation Count  Cited 9 times in Thomson Reuters Web of Science Article | Citations
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Created: Tue, 01 Sep 2009, 22:36:19 EST by Cameron Harris on behalf of School of Biomedical Sciences