T47D Cells Expressing Myeloperoxidase Are Able to Process, Traffic and Store the Mature Protein in Lysosomes: Studies in T47D Cells Reveal a Role for Cys319 in MPO Biosynthesis that Precedes Its Known Role in Inter-Molecular Disulfide Bond Formation

PloS One
Richard P LauraRichard A Maki

Abstract

Among the human heme-peroxidase family, myeloperoxidase (MPO) has a unique disulfide-linked oligomeric structure resulting from multi-step processing of the pro-protein monomer (proMPO) after it exits the endoplasmic reticulum (ER). Related family members undergo some, but not all, of the processing steps involved with formation of mature MPO. Lactoperoxidase has its pro-domain proteolytically removed and is a monomer in its mature form. Eosinophil peroxidase undergoes proteolytic removal of its pro-domain followed by proteolytic separation into heavy and light chains and is a heterodimer. However, only MPO undergoes both these proteolytic modifications and then is further oligomerized into a heterotetramer by a single inter-molecular disulfide bond. The details of how and where the post-ER processing steps of MPO occur are incompletely understood. We report here that T47D breast cancer cells stably transfected with an MPO expression plasmid are able to efficiently replicate all of the processing steps that lead to formation of the mature MPO heterotetramer. MPO also traffics to the lysosome granules of T47D cells where it accumulates, allowing in-depth immunofluorescent microscopy studies of MPO trafficking and storage for the...Continue Reading

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Citations

Apr 21, 2020·Oxidative Medicine and Cellular Longevity·Márcia Fernanda Correia Jardim PazAna Amélia de Carvalho Melo Cavalcante
Feb 7, 2018·Archives of Biochemistry and Biophysics·William M Nauseef

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Datasets Mentioned

BETA
GM130

Methods Mentioned

BETA
PCR
ELISA
transfection
immunoprecipitation
Assay
glycosylation
electron microscopy
ion exchange chromatography
phosphotransferase

Software Mentioned

GraphPad
Photoshop
GraphPad Prism

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