Molecular cloning of two novel types of peptidylarginine deiminase cDNAs from retinoic acid‐treated culture of a newborn rat keratinocyte cell line

Ishigami, Akihito; Kuramoto, Masashi; Yamada, Masao; Watanabe, Kazutada; Senshu, Tatsuo

doi:10.1016/s0014-5793(98)00893-x

Cited by 36 publications

(37 citation statements)

References 24 publications

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“…The mobility of HL-60 PAD is different from those of rat PAD types I, II, and IV, which display 72-kDa bands (data not shown). Recombinant HL-60 PAD showed similar relative activities toward BAEE and Bz-L-Arg, while PAD type IV has higher relative activity toward BAEE than to Bz-L-Arg (20). Thus HL-60 PAD seems to differ from rat type IV judging from its mobility on SDS-PAGE, its kinetic properties, and its amino acid sequence.…”

Section: Table II Kinetic Parameters Of Hpad For Synthetic Substratesmentioning

confidence: 89%

“…: 81-45-787-2214; Fax: 81-45-787-2370; E-mail: myamada@yokohama-cu.ac.jp. 1 The abbreviations used are: PAD, peptidylarginine deiminase; (20), rat PAD type II cDNA (17), rabbit anti-rat PAD type II serum (15), rabbit anti-modified citrulline IgG (24), rabbit-anti MPO serum (25), and MPO cDNA (26) were described previously.…”

Section: Methodsmentioning

confidence: 99%

“…After additions of these compounds, the cells were examined for expression of PAD. Table I summarizes (15,16,20).…”

Section: Expressions Of Pad Activity In Hl-60 Cells Induced To Differmentioning

confidence: 99%

“…Their amino acid sequences constituting 662 to 673 amino acid residues have been deduced. Recently, a novel PAD cDNA named type IV was isolated from a keratinocyte cell line from a newborn rat and rat epidermis, but the distribution of the enzyme in cells and tissues is not yet known (20,21).PAD activities in rat granulocytes and mouse peritoneal macrophages have been reported, but nothing is known about the enzyme properties or structures of the enzymes (22). We studied PAD in human myeloid leukemia HL-60 cells, which can be induced to differentiate into granulocytes by retinoic acid and into monocyte/macrophages by 1␣,25-(OH) 2 D 3 or TPA (23).…”

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Molecular Characterization of Peptidylarginine Deiminase in HL-60 Cells Induced by Retinoic Acid and 1α,25-Dihydroxyvitamin D3

Nakashima¹,

Hagiwara²,

Ishigami³

et al. 1999

Journal of Biological Chemistry

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Three types of peptidylarginine deiminase (PAD), which converts a protein arginine residue to a citrulline residue, are widely distributed in animal tissues. Little is known about PAD of hemopoietic cells. We found that PAD activity in human myeloid leukemia HL-60 cells was induced with the granulocyte-inducing agents retinoic acid and dimethyl sulfoxide and with the monocyteinducing agent 1␣,25-dihydroxyvitamin D 3 . We cloned and characterized a PAD cDNA from retinoic acid-induced cells. The cDNA was 2,238 base pairs long and encoded a 663-amino acid polypeptide. The HL-60 PAD had 50 -55% amino acid sequence identities with the three known enzymes and 73% identity with the recently cloned keratinocyte PAD. The recombinant enzyme differs in kinetic properties from the known enzymes. Immunoblotting and Northern blotting with an antiserum against the enzyme and the cDNA, respectively, showed that a protein of approximately 67 kDa increased concomitantly with increase of mRNA of approximately 2.6 kilobases during granulocyte differentiation. During monocyte differentiation the same mRNA and protein increased as in granulocyte differentiation. Neither the enzyme activity nor the protein was found in macrophageinduced cells. These results suggested that expression of the PAD gene is tightly linked to myeloid differentiation.Peptidylarginine deiminases (PADs) 1 (protein-arginine deiminase, protein L-arginine iminohydrolase, EC 3.5.3.15) are a family of post-translational modification enzymes which convert arginine residues to citrulline residues in the presence of calcium ion. Enzymatic deimination in vitro changes the functional properties of various proteins and alters their secondary and tertiary structures (1-4). Deimination of keratins, filaggrin, and trichohyalin is involved in the process of keratinization of skin and hair (4 -9). Deiminated keratins and filaggrin are found in the cornified layer of the epidermis and deiminated trichohyalin is localized in the medulla of hair and the inner root sheath of hair follicles and these modifications are tightly linked to cell-specific stages of epidermis differentiation and hair follicle development (5-9). Extensively deiminated forms of myelin basic protein are also found in normal infant brain and in demyelinated areas of brain with multiple sclerosis, and this deimination is thought to be associated with immature myelination (10, 11). We reported a correlation between deimination of vimentin in mouse peritoneal macrophages and ionomycin-induced apoptosis (12). Deimination of a 70-kDa nuclear protein in cultured keratinocytes associated with apoptosis was also reported recently (13). All these findings suggest involvements of PAD in biological as well as pathological processes. There are at least three types of PAD in various rodent tissues which seem to be cell type specific (3, 14 -16). Their substrate specificities for BAEE and Bz-L-Arg and their antigenic properties are different. PAD type II purified from rat muscle has been well characterized. It is also pres...

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Section: Table II Kinetic Parameters Of Hpad For Synthetic Substratesmentioning

confidence: 89%

Section: Methodsmentioning

confidence: 99%

“…After additions of these compounds, the cells were examined for expression of PAD. Table I summarizes (15,16,20).…”

Section: Expressions Of Pad Activity In Hl-60 Cells Induced To Differmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Molecular Characterization of Peptidylarginine Deiminase in HL-60 Cells Induced by Retinoic Acid and 1α,25-Dihydroxyvitamin D3

Nakashima¹,

Hagiwara²,

Ishigami³

et al. 1999

Journal of Biological Chemistry

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181

169

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PAD, a growing family of citrullinating enzymes: genes, features and involvement in disease

et al. 2003

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Peptidylarginine deiminase (PAD, EC 3.5.3.15) enzymes catalyze the conversion of protein-bound arginine to citrulline. This post-translational modification may have a big impact on the structure and function of the target protein. In this review, we will discuss the effects of citrullination and its involvement in several human diseases, including rheumatoid arthritis and multiple sclerosis. So far, four isotypes of PAD have been described in mammals. We describe the existence of PAD in non-mammalian vertebrates and the existence of a fifth mammalian PAD. In addition, tissue-specific expression, genomic organization and evolutionary conservation of the different PAD isotypes will be discussed in detail. This article contains supplementary material which may be viewed at the BioEssays website at http://www.interscience.wiley.com/jpages/0265-9247/suppmat/2003/25/v25.1106.html.

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Abnormal accumulation of citrullinated proteins catalyzed by peptidylarginine deiminase in hippocampal extracts from patients with Alzheimer's disease

et al. 2005

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Citrullinated proteins are the products of a posttranslational process in which arginine residues undergo modification into citrulline residues when catalyzed by peptidylarginine deiminases (PADs) in a calcium ion-dependent manner. In our previous report, PAD2 expressed mainly in the rat cerebrum became activated early in the neurodegenerative process. To elucidate the involvement of protein citrullination in human neuronal degeneration, we examined whether citrullinated proteins are produced during Alzheimer's disease (AD). By Western blot analysis with antimodified citrulline antibody, citrullinated proteins of varied molecular weights were detected in hippocampal tissues from patients with AD but not normal humans. Two of the citrullinated proteins were identified as vimentin and glial fibrillary acidic protein (GFAP) by using two-dimensional gel electrophoresis and MALDI-TOF mass spectrometry. Interestingly, PAD2 was detected in hippocampal extracts from AD and normal brains, but the amount of PAD2 in the AD tissue was markedly greater. Histochemical analysis revealed citrullinated proteins throughout the hippocampus, especially in the dentate gyrus and stratum radiatum of CA1 and CA2 areas. However, no citrullinated proteins were detected in the normal hippocampus. PAD2 immunoreactivity was also ubiquitous throughout both the AD and the normal hippocampal areas. PAD2 enrichment coincided well with citrullinated protein positivity. Double immunofluorescence staining revealed that citrullinated protein- and PAD2-positive cells also coincided with GFAP-positive cells, but not all GFAP-positive cells were positive for PAD2. As with GFAP, which is an astrocyte-specific marker protein, PAD2 is distributed mainly in astrocytes. These collective results, the abnormal accumulation of citrullinated proteins and abnormal activation of PAD2 in hippocampi of patients with AD, strongly suggest that PAD has an important role in the onset and progression of AD and that citrullinated proteins may become a useful marker for human neurodegenerative diseases.

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Molecular cloning of two novel types of peptidylarginine deiminase cDNAs from retinoic acid‐treated culture of a newborn rat keratinocyte cell line

Cited by 36 publications

References 24 publications

Molecular Characterization of Peptidylarginine Deiminase in HL-60 Cells Induced by Retinoic Acid and 1α,25-Dihydroxyvitamin D3

Molecular Characterization of Peptidylarginine Deiminase in HL-60 Cells Induced by Retinoic Acid and 1α,25-Dihydroxyvitamin D3

PAD, a growing family of citrullinating enzymes: genes, features and involvement in disease

Abnormal accumulation of citrullinated proteins catalyzed by peptidylarginine deiminase in hippocampal extracts from patients with Alzheimer's disease

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