Human UDP-Glucose Dehydrogenase Gene: Complete Cloning and Transcription Start Mapping

Bontemps, Yannick; Maquart, François‐Xavier; Wegrowski, Yanusz

doi:10.1006/bbrc.2000.3389

Cited by 7 publications

(9 citation statements)

References 15 publications

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“…Mutations in the conserved glycine residues of the loop have been correlated with attenuation or elimination of enzyme activity (50 -52) and also with disease (53). The conserved structure suggests that UGDH may be part of a minimal genome for multicellular species and that the rigid basal structure is necessary for its activity (14,42). To our knowledge, the crystallographic structure of hUGDH has not been determined, and no studies by site-directed mutagenesis for the coenzyme-binding site(s) of the mammalian UGDHs have been reported yet.…”

Section: Discussionmentioning

confidence: 99%

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Importance of Gly-13 for the Coenzyme Binding of Human UDP-glucose Dehydrogenase

Huh

Yoon²,

Lee

et al. 2004

Journal of Biological Chemistry

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UDP-glucose dehydrogenase (UGDH) is (6, 7) show that the reaction of UGDH involves two successive oxidations to convert the 6Ј-hydroxyl of UDP-glucose to a carboxylate, together with the reduction of 2 molecules of NAD ϩ to NADH. In animals, it constitutes the unique pathway for glucuronate formation (8). Because glucuronate is a component of glycosaminoglycans (GAGs), the mutation inactivation of UGDH (sugarless) abolishes GAG assembly and, consequently, abolishes GAG-dependent growth factor signaling (9 -11). The primary structure of the mammalian enzyme was obtained from the protein sequence of bovine UGDH (12). The human gene was also recently cloned and assigned to chromosome 4p15.1 (13). It contains 12 exons, extends over 26 kb, and has one major transcription start site (14).GAG chains of proteoglycans and hyaluronan are ubiquitous components of extracellular matrix and pericellular spaces. There is a growing body of information on the implication of GAGs in cell behavior, including signal transduction, cell proliferation, spreading, migration, and cancer growth and metastasis (15-17). GAG synthesis is influenced by cytokines and growth factors. Transforming growth factor-␤ is the most potent stimulator of proteoglycan and GAG synthesis, including that of hyaluronan. Its action, however, depends on the cell type (18). The synthesis of GAGs is also modulated by oxygen cell status. Hypoxic endothelial cells and lung fibroblasts enhanced the heparan sulfate/chondroitin sulfate ratio, which led to an increase of basic fibroblast growth factor reactivity on the cell surface (19,20). It was also shown that the level of intracellular UDP-glucuronate could influence GAG synthesis (8). Interestingly, the human UGDH was shown to be an early response gene after interleukin-1 treatment of ocular fibroblasts (21), as well as an early androgen response gene in breast cancer (22).Although a clone of human UGDH has been reported (13, 15), specific catalytic residues are not yet available. Therefore, further characterization of the active sites of human UGDH is needed to elucidate the physiological nature of the UGDH. In the present study, we have identified an NAD ϩ -binding site using photoaffinity labeling and cassette mutagenesis to gain a deeper insight into the structural basis of human UGDH. For this study, a 1509-base pair gene that encodes human UGDH has been chemically synthesized and expressed in Escherichia coli as a soluble protein. Identification of the nucleotide-binding sites of a variety of proteins has been advanced by the use of nucleotide photoaffinity analogues that selectively insert * This work was supported by Grant 03-PJ1-PG3-20900-0047 from the Korea Health 21 R&D Project, Ministry of Health and Welfare, Korea (to S.-W. C.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.The nucleotide sequence (s)

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Section: Discussionmentioning

confidence: 99%

“…The human gene was also recently cloned and assigned to chromosome 4p15.1 (13). It contains 12 exons, extends over 26 kb, and has one major transcription start site (14).…”

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confidence: 99%

Importance of Gly-13 for the Coenzyme Binding of Human UDP-glucose Dehydrogenase

Huh

Yoon²,

Lee

et al. 2004

Journal of Biological Chemistry

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“…The blot was hybridized with a 165-bp probe containing the 5Ј portion of UGDH cDNA (6). A 3-kb fragment, which gave a weak hybridization band with the probe, was excised from the gel, subcloned into a pBluescript plasmid, and fully sequenced.…”

Section: Methodsmentioning

confidence: 99%

“…The primary structure of the mammalian enzyme was obtained from the protein sequence of bovine UGDH (5). The human gene, recently cloned in our laboratory (6), was assigned to chromosome 4p15.1 by radiation hybrid mapping (7). It contains 12 exons, extends over 26 kb, and has one major transcription start site (6).…”

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Specific Protein-1 Is a Universal Regulator of UDP-glucose Dehydrogenase Expression

Bontemps

Vuillermoz

Antonicelli

et al. 2003

Journal of Biological Chemistry

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UDP-Glucose 6-Dehydrogenase (UGDH)

Wegrowski

Pitsillides

2014

Handbook of Glycosyltransferases and Related Genes

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Recent advances in the field of immuno-oncology have brought transformative changes in the management of cancer patients. The immune profile of tumours has been found to have key value in predicting disease prognosis and treatment response in various cancers. Multiplex immunohistochemistry and immunofluorescence have emerged as potent tools for the simultaneous detection of multiple protein biomarkers in a single tissue section, thereby expanding opportunities for molecular and immune profiling while preserving tissue samples. By establishing the phenotype of individual tumour cells when distributed within a mixed cell population, the identification of clinically relevant biomarkers with high-throughput multiplex immunophenotyping of tumour samples has great potential to guide appropriate treatment choices. Moreover, the emergence of novel multi-marker imaging approaches can now provide unprecedented insights into the tumour microenvironment, including the potential interplay between various cell types. However, there are significant challenges to widespread integration of these technologies in daily research and clinical practice. This review addresses the challenges and potential solutions within a structured framework of action from a regulatory and clinical trial perspective. New developments within the field of immunophenotyping using multiplexed tissue imaging platforms and associated digital pathology are also described, with a specific focus on translational implications across different subtypes of cancer.

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Human UDP-Glucose Dehydrogenase Gene: Complete Cloning and Transcription Start Mapping

Cited by 7 publications

References 15 publications

Importance of Gly-13 for the Coenzyme Binding of Human UDP-glucose Dehydrogenase

Importance of Gly-13 for the Coenzyme Binding of Human UDP-glucose Dehydrogenase

Specific Protein-1 Is a Universal Regulator of UDP-glucose Dehydrogenase Expression

UDP-Glucose 6-Dehydrogenase (UGDH)

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