Molecular Phylogeny and Functional Genomics of β-Galactoside α2,6-Sialyltransferases That Explain Ubiquitous Expression of st6gal1 Gene in Amniotes

Petit, Daniel; Mir, Anne-Marie; Petit, Jean‐Michel; Thisse, Christine; Delannoy, Philippe; Oriol, Rafaël; Thisse, Bernard; Harduin-Lepers, Anne

doi:10.1074/jbc.m110.163931

Cited by 24 publications

(40 citation statements)

References 117 publications

(112 reference statements)

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“…These sequences showed a metazoan taxonomic affiliation based on the occurrence of conserved sialylmotifs L, S, III, and VS and could be related to st3gal gene family based on BLAST analysis, but no st3gal family motif ( Patel and Balaji 2006 ; Harduin-Lepers 2010 ) was detected in these sequences and thus, they were not included in this study. Although the evolutionary relationships between all the sialyltransferase families are not yet established, the st3gal as well as the st6gal gene ( Petit et al 2010 ) families could represent the most ancient sialyltransferase families described in animals with major role in metazoan evolution. To obtain the enlarged view on the evolution of the α2,3-sialylation machinery in metazoan illustrated in figure 8 , we first reconstructed the molecular phylogeny of ST3Gal-related sequences.…”

Section: Discussionmentioning

confidence: 99%

“…A seminal work reported on the ancient occurrence of sialyltransferase-related genes in “basal” metazoan species, much sooner than previously anticipated and the sudden emergence of several new sialyltransferase sequences more or less retained in the various vertebrate lineages ( Harduin-Lepers et al 2005 ; Varki 2006 , 2011 ). Two of the four sialyltransferase multigene families (e.g., ST8Sia and ST6Gal) were subjected to phylogenetic reconstructions in the context of the two rounds of whole-genome duplication (2R-WGD) events that occurred in early vertebrates ( Ohno 1970 ) shedding new light into the key genetic events underpinning the establishment of α2,6- and α2,8-sialylation machineries ( Harduin-Lepers et al 2008 ; Petit et al 2010 , 2013 ). Almost nothing is known pertaining to the origin and evolutionary history of two remaining sialyltransferase families (e.g., ST6GalNAc and ST3Gal).…”

Section: Introductionmentioning

confidence: 99%

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Integrative View of α2,3-Sialyltransferases (ST3Gal) Molecular and Functional Evolution in Deuterostomes: Significance of Lineage-Specific Losses

Petit

Teppa

Mir

et al. 2014

Molecular Biology and Evolution

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Sialyltransferases are responsible for the synthesis of a diverse range of sialoglycoconjugates predicted to be pivotal to deuterostomes’ evolution. In this work, we reconstructed the evolutionary history of the metazoan α2,3-sialyltransferases family (ST3Gal), a subset of sialyltransferases encompassing six subfamilies (ST3Gal I–ST3Gal VI) functionally characterized in mammals. Exploration of genomic and expressed sequence tag databases and search of conserved sialylmotifs led to the identification of a large data set of st3gal-related gene sequences. Molecular phylogeny and large scale sequence similarity network analysis identified four new vertebrate subfamilies called ST3Gal III-r, ST3Gal VII, ST3Gal VIII, and ST3Gal IX. To address the issue of the origin and evolutionary relationships of the st3gal-related genes, we performed comparative syntenic mapping of st3gal gene loci combined to ancestral genome reconstruction. The ten vertebrate ST3Gal subfamilies originated from genome duplication events at the base of vertebrates and are organized in three distinct and ancient groups of genes predating the early deuterostomes. Inferring st3gal gene family history identified also several lineage-specific gene losses, the significance of which was explored in a functional context. Toward this aim, spatiotemporal distribution of st3gal genes was analyzed in zebrafish and bovine tissues. In addition, molecular evolutionary analyses using specificity determining position and coevolved amino acid predictions led to the identification of amino acid residues with potential implication in functional divergence of vertebrate ST3Gal. We propose a detailed scenario of the evolutionary relationships of st3gal genes coupled to a conceptual framework of the evolution of ST3Gal functions.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Integrative View of α2,3-Sialyltransferases (ST3Gal) Molecular and Functional Evolution in Deuterostomes: Significance of Lineage-Specific Losses

Petit

Teppa

Mir

et al. 2014

Molecular Biology and Evolution

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“…[10][11][12][13] In contrast to ST6GAL1, ST6GAL2, a recently identified sialyltransferase, is confined to human intestine, colon, and brain. 14,15 A tremendous number of studies have focused on the involvement of ST6GAL2 in tumorigenesis, such as follicular thyroid carcinoma 16 and melanoma. 17 However, the role of ST6GAL2 in breast cancer is still unclear.…”

Section: Introductionmentioning

confidence: 99%

<p>ST6GAL2 Downregulation Inhibits Cell Adhesion and Invasion and is Associated with Improved Patient Survival in Breast Cancer</p>

Cheng¹,

Wang²,

Zhong³

et al. 2020

OTT

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These authors contributed equally to this workObjective: Breast cancer is one of the most common and serious types of cancer, with a particularly unfavorable prognosis. Although dysregulation of β-galactoside α 2,6-sialyltransferase 2 (ST6GAL2) has been observed in multiple cancers, the mechanism involved remains to be clarified. In this study, we focused on the potential function of ST6GAL2 in the regulation of breast cancer. Methods: Flow cytometry and CCK-8 were used to measure markers of the cell cycle proliferation, adhesion, and invasion. Real-time PCR and immunohistochemistry analysis were used to detect the expression levels of ST6GAL2 in breast cancer tissues. Western blot was used to analyze the expression level of genes correlated with focal adhesion and metastasis pathways in breast cancer cells. Results: ST6GAL2 expression levels were higher in breast cancer tissues as compared to healthy tissues. ST6GAL2 expression was associated with tumor stage, survival time, and estrogen receptor (ER)/progesterone receptor (PR)/human epidermal growth factor receptor 2 (HER2) status of breast cancer patients. Silence of ST6GAL2 inhibited cancer progression by arresting cell cycle progression at G0/G1 phase and inhibiting cell adhesion and invasion. ST6GAL2 was positively correlated with focal adhesion and metastasis pathways, and its downregulation inhibited the expression of ICAM-1, VCAM-1, CD24, MMP2, MMP9, and CXCR4. Conclusion: These findings indicated that ST6GAL2 might serve as a useful potential target for treatment of breast cancer.

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“…Only eukaryotic core α1,6-FucT sequences were considered for this study. Homologous fut8 sequences were searched by querying all genomic and expressed sequence tag (EST) divisions of the National Center for Biotechnology Information (NCBI database, Washington, DC, USA), as described previously for sialyltransferases [22] , [64] ( Table S2 ). DNA and aa sequences were analyzed using DNA Strider [65] .…”

Section: Methodsmentioning

confidence: 99%

“…The absence of complex oligosaccharides correlates with the absence of β1,4-galactosyltransferase I (β1,4GalTI) [20] , [21] and sialyltransferases [18] . Despite the in silico identification of α2,6-sialyltransferase ( st6gal ) gene sequences in some lepidopterans, such as Bombyx mori [22] , no sialyltransferase activity has been detected in insect cell lines, such as Sf 9 ( S. frugiperda ) cells [18] , [23] . In addition, the very low expression level of N - acetylglucosaminyltransferase I (GNT-I) [18] , [24] , [25] and GNT-II [26] and the presence of a Golgi-associated N -acetylglucosaminidase (FDL) [27] , [28] explain the formation of paucimannose structures.…”

Section: Introductionmentioning

confidence: 99%

The α1,6-Fucosyltransferase Gene (fut8) from the Sf9 Lepidopteran Insect Cell Line: Insights into fut8 Evolution

Juliant¹,

Harduin-Lepers

Monjaret³

et al. 2014

PLoS ONE

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The core alpha1,6-fucosyltransferase (FUT8) catalyzes the transfer of a fucosyl moiety from GDP-fucose to the innermost asparagine-linked N-acetylglucosamine residue of glycoproteins. In mammals, this glycosylation has an important function in many fundamental biological processes and although no essential role has been demonstrated yet in all animals, FUT8 amino acid (aa) sequence and FUT8 activity are very well conserved throughout the animal kingdom. We have cloned the cDNA and the complete gene encoding the FUT8 in the Sf9 (Spodoptera frugiperda) lepidopteran cell line. As in most animal genomes, fut8 is a single-copy gene organized in different exons. The open reading frame contains 12 exons, a characteristic that seems to be shared by all lepidopteran fut8 genes. We chose to study the gene structure as a way to characterize the evolutionary relationships of the fut8 genes in metazoans. Analysis of the intron-exon organization in 56 fut8 orthologs allowed us to propose a model for fut8 evolution in metazoans. The presence of a highly variable number of exons in metazoan fut8 genes suggests a complex evolutionary history with many intron gain and loss events, particularly in arthropods, but not in chordata. Moreover, despite the high conservation of lepidoptera FUT8 sequences also in vertebrates and hymenoptera, the exon-intron organization of hymenoptera fut8 genes is order-specific with no shared exons. This feature suggests that the observed intron losses and gains may be linked to evolutionary innovations, such as the appearance of new orders.

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Molecular Phylogeny and Functional Genomics of β-Galactoside α2,6-Sialyltransferases That Explain Ubiquitous Expression of st6gal1 Gene in Amniotes

Cited by 24 publications

References 117 publications

Integrative View of α2,3-Sialyltransferases (ST3Gal) Molecular and Functional Evolution in Deuterostomes: Significance of Lineage-Specific Losses

Integrative View of α2,3-Sialyltransferases (ST3Gal) Molecular and Functional Evolution in Deuterostomes: Significance of Lineage-Specific Losses

<p>ST6GAL2 Downregulation Inhibits Cell Adhesion and Invasion and is Associated with Improved Patient Survival in Breast Cancer</p>

The α1,6-Fucosyltransferase Gene (fut8) from the Sf9 Lepidopteran Insect Cell Line: Insights into fut8 Evolution

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