The C-terminus of rat <scp>L</scp>-histidine decarboxylase specifically inhibits enzymic activity and disrupts pyridoxal phosphate-dependent interactions with <scp>L</scp>-histidine substrate analogues

Fleming, John; Fajardo, Ignacio; Langlois, Michael R.; Sánchez‐Jiménez, Francisca; Wang, Yichen

doi:10.1042/bj20031553

Cited by 29 publications

(16 citation statements)

References 40 publications

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“…At least in Cos-7-transfected cells, several HDC immunoreactive bands ranging from 63-36 kDa are generated from the full-length open reading frame. (64) It would be interesting to know the minimum fragment able to be active in vivo. The limit for this C-terminal processing is known to be between residues 472 and 477.…”

Section: Processingmentioning

confidence: 99%

Mammalian histidine decarboxylase: from structure to function

2004

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Histamine is a multifunctional biogenic amine with relevant roles in intercellular communication, inflammatory processes and highly prevalent pathologies. Histamine biosynthesis depends on a single decarboxylation step, carried out by a PLP-dependent histidine decarboxylase activity (EC 4.1.1.22), an enzyme that still remains to be fully characterized. Nevertheless, during the last few years, important advances have been made in this field, including the generation and validation of the first three-dimensional model of the enzyme, which allows us to revisit previous results and conclusions. This essay provides a comprehensive review of the current knowledge of the structural and functional characteristics of mammalian histidine decarboxylase.

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Section: Processingmentioning

confidence: 99%

Mammalian histidine decarboxylase: from structure to function

2004

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“…Because caspase family and granzyme B have been found to require an aspartate residue at the cleavage site, we then investigated whether purified caspase or granzyme B has a potential to cleave HDC protein in vitro. A band, of which molecular mass is ϳ53-kDa, was detected when the 35 S-radiolabeled 74-kDa form of HDC was incubated with caspase-9 (Fig. 4).…”

Section: Post-translational Cleavage Of Hdc In P-815 Cells Treatedmentioning

confidence: 99%

“…We previously demonstrated by immunoprecipitation of the nascent 35 S-labeled HDC that the 74-kDa form is localized in the cytosol and ER while the 53-kDa form in the granule fraction in a rat mast cell line, RBL-2H3 (19). In this cell line, histamine synthesis was detected both in the cytosol and in the granule fraction.…”

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Activation of Histidine Decarboxylase through Post-translational Cleavage by Caspase-9 in a Mouse Mastocytoma P-815

Furuta

Nakayama

Sugimoto

et al. 2007

Journal of Biological Chemistry

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L-Histidine decarboxylase (HDC) is the rate-limiting enzyme for histamine synthesis in mammals. Although accumulating evidence has indicated the post-translational processing of HDC, it remains unknown what kinds of proteases are involved. We investigated the processing of HDC in a mouse mastocytoma, P-815, using a lentiviral expression system. HDC was expressed as a 74-kDa precursor form, which is cleaved to yield the 55-and 60-kDa forms upon treatment with butyrate. Alanine-scanning mutations revealed that two tandem aspartate residues (Asp 517 -Asp 518 , Asp 550 -Asp 551 ) are critical for the processing. Treatment with butyrate caused an increase in the enzyme activity of the cells expressing the wild type HDC, but not in the cells expressing the processing-incompetent mutant. An increase in histamine synthesis by butyrate was accompanied by formation of the 55-and 60-kDa form of HDC. In addition, the in vitro translated 74-kDa form of HDC was found to undergo a limited cleavage by purified human caspase-9, whereas the alanine-substituted mutants were not. Processing and enzymatic activation of HDC in P-815 cells was enhanced in the presence of a Zn 2؉ chelator, TPEN. Although treatment with butyrate and TPEN drastically augmented the protease activity of caspase-3, and -9, no apoptotic cell death was observed. Both enzymatic activation and processing of HDC were completely suppressed by a pan-caspase inhibitor, partially but significantly by a specific inhibitor for caspase-9, but not by a caspase-3 inhibitor. These results suggest that, in P-815 cells, histamine synthesis is augmented through the post-translational cleavage of HDC, which is mediated by caspase-9.Histamine plays diverse roles in physiological and pathological responses, such as inflammation, gastric acid secretion, neurotransmission, and immune modulation, by acting on its specific membrane receptors, H 1 , H 2 , H 3 , and H 4 (1-7). L-Histidine decarboxylase (HDC, 2 EC 4.1.1.22) is the rate-limiting enzyme for histamine synthesis in mammals, and targeted disruption of mouse HDC gene resulted in the complete loss of de novo synthesis of histamine (8). Several groups purified HDC from various sources including a mouse mastocytoma, P-815, indicating that purified HDC is a homodimer consisting of a 53-55-kDa subunit (9 -11). In 1990, Joseph et al. (12) succeeded in cDNA cloning of rat HDC for the first time, and demonstrated that the HDC cDNA encodes a protein, of which the molecular mass is 74 kDa. Subsequent cDNA cloning from P-815 cells revealed that mouse HDC cDNA also encodes a 74-kDa protein (13). These results indicate that HDC is initially translated as a 74-kDa form and then converted into the 53-55-kDa form through the post-translational processing. HDC belongs in the fold type I pyridoxal phosphate-dependent enzyme (13,14). Although the region around the active lysine residue of HDC shows homology with the other enzymes in this group, such as the aromatic L-amino acid decarboxylase and glutamate decarboxylase, the C-terminal 20-kDa ...

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“…However, in adult mammals, HDC is highly expressed in enterochromaffin-like (ECL) cells of the stomach, where HDC activity is tightly regulated by a gut peptide hormone, gastrin (22). HDC regulation occurs at both transcriptional and posttranslational levels, with the latter by proteolytic processing through the ubiquitin-proteasome pathway (11,12,18).HDC promoter activity is upregulated by several different stimuli, including gastrin (45), PMA (21,22,32,45), oxidative stress (20), thrombopointin (34), Helicobacter pylori infection (43,44), and by neural peptide pituitary adenylate cyclaseactivating polypeptide (PACAP) in PC12 cells through a cis element located at the Ϫ177-to Ϫ170-bp (relative to the transcriptional start site) region of the HDC promoter (30). Recently, Kruppel-like factor 4 (KLF4), formerly known as gut-enriched Kruppel-like factor, was shown to inhibit HDC promoter activity through three elements: an upstream GC box and two downstream gastrin-responsive elements (1), both of which are GC-rich sequences.…”

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Yin yang 1 (YY1) represseshistidine decarboxylasegene expression with SREBP-1a in part through an upstream Sp1 site

Ai¹,

Liu²,

Wang³

2006

American Journal of Physiology-Gastrointestinal and Liver Physi

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Histidine decarboxylase (HDC) is the enzyme that converts histidine to histamine, a bioamine that plays an important role in many physiological aspects including allergic responses, inflammation, neurotransmission, and gastric acid secretion. In previous studies, we demonstrated that Kruppel-like factor 4 represses HDC promoter activity in a gastric cell line through both an upstream Sp1-binding GC box (GGGCGG sequence) and downstream gastrin-responsive elements. In the current study, Yin Yang 1 (YY1), a pleiotropic transcriptional factor, was also shown in cotransfection assays to repress HDC promoter activity through the upstream GC box. DNA affinity purification assay demonstrated that YY1 was pulled down specifically by the upstream GC box. In addition, sterol-responsive element-binding protein 1a (SREBP-1a), a transcriptional factor that binds YY1, represses the HDC promoter. Interestingly, deletion analysis and cotransfection assays indicated that mutation of the upstream GC box or truncation of downstream gastrin-responsive elements in the HDC promoter disrupted the inhibitory effect of YY1 and SREBP-1a in an identical fashion. Furthermore, quantitative real-time PCR analysis indicated that gastrin treatment downregulated SREBP-1a gene expression and reduced the DNA binding activity of SREBP in EMSAs. Taken together, these results suggest that YY1 and SREBP-1a form a complex to inhibit HDC gene expression through both the upstream GC box and downstream gastrin-responsive elements and gastrin-induced activation of HDC gene expression is mediated at least partly through downregulation of transcriptional repressors such as SREBPs.

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The C-terminus of rat L-histidine decarboxylase specifically inhibits enzymic activity and disrupts pyridoxal phosphate-dependent interactions with L-histidine substrate analogues

Cited by 29 publications

References 40 publications

Mammalian histidine decarboxylase: from structure to function

Mammalian histidine decarboxylase: from structure to function

Activation of Histidine Decarboxylase through Post-translational Cleavage by Caspase-9 in a Mouse Mastocytoma P-815

Yin yang 1 (YY1) represseshistidine decarboxylasegene expression with SREBP-1a in part through an upstream Sp1 site

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