|
|
 Previous Article | Table of Contents | Next Article 
Myeloperoxidase biosynthesis by a human promyelocytic leukemia cell line:
insight into myeloperoxidase deficiency
WM Nauseef
The biosynthesis and processing of myeloperoxidase (MPO), a cationic enzyme
present in the azurophilic granules of human polymorphonuclear leukocytes
(PMNs), were studied in the human promyelocytic leukemia cell line, HL-60.
HL-60 cells produce large quantities of enzymatically active MPO that has
the same electrophoretic behavior as MPO isolated from normal PMNs. Mature
MPO is a glycoprotein of approximately 150,000 molecular weight (mol wt)
composed of two heavy-light protomers (alpha 2 beta 2) with subunits of
59,000 and 13,500 mol wt, respectively, under reducing conditions. The
primary translation product of MPO messenger RNA (mRNA) isolated from HL-60
cells was a single polypeptide of mol wt 80,000. In HL-60 cells labeled
with [35S]-methionine, the labeled MPO isolated by immunoprecipitation had
a mol wt of 89,000. Treatment of this 89-kilodalton (kDa) species with
endoglycosidase H produced a 79-kDa peptide, suggesting that the 89-kDa
protein contained high-mannose side chains. The 89-kDa species had no
detectable peroxidase activity. During chase experiments some of the 89-kDa
peptide was processed to smaller species of mol wt 39,000, 59,000, and
13,500, although a fraction of the 89-kDa peptide remained unprocessed
after a chase of 100 hours. In addition, a small amount of the 89-kDa
peptide appeared in the medium without any of the processed smaller
peptides. These studies suggest that the primary translation product in MPO
biosynthesis is an 80-kDa peptide that undergoes cotranslational cleavage
of the signal peptide and glycosylation to produce an 89-kDa pro-MPO, that
pro-MPO is a single polypeptide containing the alpha and beta subunits of
MPO and contains endoglycosidase H-susceptible high- mannose side chains,
and that posttranslational modification of pro-MPO results in targeting to
the lysosome and proteolytic maturation of pro- MPO to active enzyme. In
light of the previous observation that MPO- deficient and normal PMNs
contain an 89-kDa protein immunochemically related to MPO, these studies on
MPO biosynthesis indirectly support the hypothesis that defective
posttranslation processing by pro-MPO may underlie hereditary MPO
deficiency.
Volume 67,
Issue 4,
pp. 865-872,
04/01/1986
Copyright © 1986 by The American Society of Hematology
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
M. Goedken, S. McCormick, K. G. Leidal, K. Suzuki, Y. Kameoka, J. M. Astern, M. Huang, A. Cherkasov, and W. M. Nauseef
Impact of Two Novel Mutations on the Structure and Function of Human Myeloperoxidase
J. Biol. Chem.,
September 21, 2007;
282(38):
27994 - 28003.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. J. Reszka, B. A. Wagner, L. M. Teesch, B. E. Britigan, D. R. Spitz, and C. P. Burns
Inactivation of Anthracyclines by Cellular Peroxidase
Cancer Res.,
July 15, 2005;
65(14):
6346 - 6353.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Reumaux, M. de Boer, A. B. Meijer, P. Duthilleul, and D. Roos
Expression of myeloperoxidase (MPO) by neutrophils is necessary for their activation by anti-neutrophil cytoplasm autoantibodies (ANCA) against MPO
J. Leukoc. Biol.,
June 1, 2003;
73(6):
841 - 849.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. A. Clark, S.-L. Li, D. W. Pearson, K. G. Leidal, J. R. Clark, G. M. Denning, R. Reddick, K.-H. Krause, and A. J. Valente
Regulation of Calreticulin Expression during Induction of Differentiation in Human Myeloid Cells. EVIDENCE FOR REMODELING OF THE ENDOPLASMIC RETICULUM
J. Biol. Chem.,
August 23, 2002;
277(35):
32369 - 32378.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. M. Nauseef, S. J. McCormick, and M. Goedken
Coordinated Participation of Calreticulin and Calnexin in the Biosynthesis of Myeloperoxidase
J. Biol. Chem.,
March 20, 1998;
273(12):
7107 - 7111.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Andersson, L. Hellman, U. Gullberg, and I. Olsson
The Role of the Propeptide for Processing and Sorting of Human Myeloperoxidase
J. Biol. Chem.,
February 20, 1998;
273(8):
4747 - 4753.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Romano, P. Dri, L. Dadalt, P. Patriarca, and F. E. Baralle
Biochemical and Molecular Characterization of Hereditary Myeloperoxidase Deficiency
Blood,
November 15, 1997;
90(10):
4126 - 4134.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. M. Denning, K. G. Leidal, V. A. Holst, S. S. Iyer, D. W. Pearson, J. R. Clark, W. M. Nauseef, and R. A. Clark
Calreticulin Biosynthesis and Processing in Human Myeloid Cells: Demonstration of Signal Peptide Cleavage and N-Glycosylation
Blood,
July 1, 1997;
90(1):
372 - 381.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
V. Le Cabec, J. Calafat, and N. Borregaard
Sorting of the Specific Granule Protein, NGAL, During Granulocytic Maturation of HL-60 Cells
Blood,
March 15, 1997;
89(6):
2113 - 2121.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. M. Nauseef, M. Cogley, and S. McCormick
Effect of the R569W Missense Mutation on the Biosynthesis of Myeloperoxidase
J. Biol. Chem.,
April 19, 1996;
271(16):
9546 - 9549.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. M. Nauseef, S. J. McCormick, and R. A. Clark
Calreticulin Functions as a Molecular Chaperone in the Biosynthesis of Myeloperoxidase
J. Biol. Chem.,
March 3, 1995;
270(9):
4741 - 4747.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. A. Wagner, G. R. Buettner, L. W. Oberley, C. J. Darby, and C. P. Burns
Myeloperoxidase Is Involved in H2O2-induced Apoptosis of HL-60 Human Leukemia Cells
J. Biol. Chem.,
July 14, 2000;
275(29):
22461 - 22469.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
