Unknown

Dataset Information

0

Peptidyl-prolyl cis/trans-isomerase A1 (Pin1) is a target for modification by lipid electrophiles.


ABSTRACT: Oxidation of membrane phospholipids is associated with inflammation, neurodegenerative disease, and cancer. Oxyradical damage to phospholipids results in the production of reactive aldehydes that adduct proteins and modulate their function. 4-Hydroxynonenal (HNE), a common product of oxidative damage to lipids, adducts proteins at exposed Cys, His, or Lys residues. Here, we demonstrate that peptidyl-prolyl cis/trans-isomerase A1 (Pin1), an enzyme that catalyzes the conversion of the peptide bond of pSer/pThr-Pro moieties in signaling proteins from cis to trans, is highly susceptible to HNE modification. Incubation of purified Pin1 with HNE followed by MALDI-TOF/TOF mass spectrometry resulted in detection of Michael adducts at the active site residues His-157 and Cys-113. Time and concentration dependencies indicate that Cys-113 is the primary site of HNE modification. Pin1 was adducted in MDA-MB-231 breast cancer cells treated with 8-alkynyl-HNE as judged by click chemistry conjugation with biotin followed by streptavidin-based pulldown and Western blotting with anti-Pin1 antibody. Furthermore, orbitrap MS data support the adduction of Cys-113 in the Pin1 active site upon HNE treatment of MDA-MB-231 cells. siRNA knockdown of Pin1 in MDA-MB-231 cells partially protected the cells from HNE-induced toxicity. Recent studies indicate that Pin1 is an important molecular target for the chemopreventive effects of green tea polyphenols. The present study establishes that it is also a target for electrophilic modification by products of lipid peroxidation.

SUBMITTER: Aluise CD 

PROVIDER: S-EPMC3579456 | biostudies-literature | 2013 Feb

REPOSITORIES: biostudies-literature

altmetric image

Publications

Peptidyl-prolyl cis/trans-isomerase A1 (Pin1) is a target for modification by lipid electrophiles.

Aluise Christopher D CD   Rose Kristie K   Boiani Mariana M   Reyzer Michelle L ML   Manna Joseph D JD   Tallman Keri K   Porter Ned A NA   Marnett Lawrence J LJ  

Chemical research in toxicology 20121224 2


Oxidation of membrane phospholipids is associated with inflammation, neurodegenerative disease, and cancer. Oxyradical damage to phospholipids results in the production of reactive aldehydes that adduct proteins and modulate their function. 4-Hydroxynonenal (HNE), a common product of oxidative damage to lipids, adducts proteins at exposed Cys, His, or Lys residues. Here, we demonstrate that peptidyl-prolyl cis/trans-isomerase A1 (Pin1), an enzyme that catalyzes the conversion of the peptide bond  ...[more]

Similar Datasets

| S-EPMC7243138 | biostudies-literature
| S-EPMC7113879 | biostudies-literature
| S-EPMC2748248 | biostudies-literature
| S-EPMC5986602 | biostudies-literature
| S-EPMC6539592 | biostudies-literature
| S-EPMC1540071 | biostudies-literature
| S-EPMC7064559 | biostudies-literature
| S-EPMC1618848 | biostudies-literature
| S-EPMC10315659 | biostudies-literature
| S-EPMC3892300 | biostudies-literature