Lectins as mitosis stimulating factors: Briefly reviewed

Carvalho, Elba Verônica Matoso Maciel de; Oliveira, Weslley Felix de; Coelho, Luana Cassandra Breitenbach Barroso; Correia, Maria T.S.

doi:10.1016/j.lfs.2018.06.003

Cited by 32 publications

(25 citation statements)

References 70 publications

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“…The mitogenic effects of certain lectins were first reported in 1960 by Nowell, who described the ability of the plant lectin phytohemagglutinin (PHA) to induce the growth and division of lymphocytes 10 . Lectins exert their mitogenic activity through multiple mechanisms, including binding to T cell receptors (TCRs) and inducing second messenger-mediated stimulation and production of pro-proliferation cytokines 11,12 . Indeed, this property of lectins has been utilized by the scientific community to study mechanisms of immune activation, immunodeficiencies, and malignancies, and in other applications such as growing retroviruses.…”

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confidence: 99%

Targeted disruption of pi–pi stacking in Malaysian banana lectin reduces mitogenicity while preserving antiviral activity

Covés-Datson

King

Legendre

et al. 2021

Sci Rep

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Lectins, carbohydrate-binding proteins, have been regarded as potential antiviral agents, as some can bind glycans on viral surface glycoproteins and inactivate their functions. However, clinical development of lectins has been stalled by the mitogenicity of many of these proteins, which is the ability to stimulate deleterious proliferation, especially of immune cells. We previously demonstrated that the mitogenic and antiviral activities of a lectin (banana lectin, BanLec) can be separated via a single amino acid mutation, histidine to threonine at position 84 (H84T), within the third Greek key. The resulting lectin, H84T BanLec, is virtually non-mitogenic but retains antiviral activity. Decreased mitogenicity was associated with disruption of pi–pi stacking between two aromatic amino acids. To examine whether we could provide further proof-of-principle of the ability to separate these two distinct lectin functions, we identified another lectin, Malaysian banana lectin (Malay BanLec), with similar structural features as BanLec, including pi–pi stacking, but with only 63% amino acid identity, and showed that it is both mitogenic and potently antiviral. We then engineered an F84T mutation expected to disrupt pi–pi stacking, analogous to H84T. As predicted, F84T Malay BanLec (F84T) was less mitogenic than wild type. However, F84T maintained strong antiviral activity and inhibited replication of HIV, Ebola, and other viruses. The F84T mutation disrupted pi–pi stacking without disrupting the overall lectin structure. These findings show that pi–pi stacking in the third Greek key is a conserved mitogenic motif in these two jacalin-related lectins BanLec and Malay BanLec, and further highlight the potential to rationally engineer antiviral lectins for therapeutic purposes.

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confidence: 99%

Targeted disruption of pi–pi stacking in Malaysian banana lectin reduces mitogenicity while preserving antiviral activity

Covés-Datson

King

Legendre

et al. 2021

Sci Rep

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“…Many plant lectins have been shown to affect the cell cycle [49]. Some lectins are able to bind to growth factor receptor glycans on the cell surface.…”

Section: Discussionmentioning

confidence: 99%

The lectin ArtinM activates RBL-2H3 mast cells without inducing degranulation

et al. 2020

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Mast cells are connective tissue resident cells with morphological and functional characteristics that contribute to their role in allergic and inflammatory processes, host defense and maintenance of tissue homeostasis. Mast cell activation results in the release of pro-inflammatory mediators which are largely responsible for the physiological functions of mast cells. The lectin ArtinM, extracted from Artocarpus heterophyllus (jackfruit), binds to D-manose, thus inducing degranulation of mast cells. ArtinM has several immunomodulatory properties including acceleration of wound healing, and induction of cytokine release. The aim of the present study was to investigate the role of ArtinM in the activation and proliferation of mast cells. The rat mast cell line RBL-2H3 was used throughout this study. At a low concentration (0.25μg/mL), ArtinM induced mast cell activation and the release of IL-6 without stimulating the release of pre-formed or newly formed mediators. Additionally, when the cells were activated by ArtinM protein tyrosine phosphorylation was stimulated. The low concentration of ArtinM also activated the transcription factor NFkB, but not NFAT. ArtinM also affected the cell cycle and stimulated cell proliferation. Therefore, ArtinM may have therapeutic applications by modulating immune responses due to its ability to activate mast cells and promote the release of newly synthesized mediators. Additionally, ArtinM could have beneficial effects at low concentrations without degranulating mast cells and inducing allergic reactions.

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“…These structurally different molecules pertain to different protein families, such as galectin [2], C-type [3,4], SUEL/RBL-type [5,6], R-type [7], and HSP110-type [8] lectins. Numerous studies have reported that invertebrate lectins are able to inhibit or to promote mammalian cell growth [9,10,11,12]. Moreover, some lectins are capable of killing carcinoma cells and microorganisms through the binding to N-acetylhexosamines, such as N-acetyl D-galactosamine (GalNAc), N-acetyl D-glucosamine (GlcNAc), N-acetyl D-mannosamine (ManNAc) and N-acetylneuramic acid (NeuAc) which in turn activates signal transduction, leading to cell death.…”

Section: Introductionmentioning

confidence: 99%

Functional Characterization of OXYL, A SghC1qDC LacNAc-specific Lectin from The Crinoid Feather Star Anneissia Japonica

et al. 2019

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We identified a lectin (carbohydrate-binding protein) belonging to the complement 1q(C1q) family in the feather star Anneissia japonica (a crinoid pertaining to the phylum Echinodermata). The combination of Edman degradation and bioinformatics sequence analysis characterized the primary structure of this novel lectin, named OXYL, as a secreted 158 amino acid-long globular head (sgh)C1q domain containing (C1qDC) protein. Comparative genomics analyses revealed that OXYL pertains to a family of intronless genes found with several paralogous copies in different crinoid species. Immunohistochemistry assays identified the tissues surrounding coelomic cavities and the arms as the main sites of production of OXYL. Glycan array confirmed that this lectin could quantitatively bind to type-2 N-acetyllactosamine (LacNAc: Galβ1-4GlcNAc), but not to type-1 LacNAc (Galβ1-3GlcNAc). Although OXYL displayed agglutinating activity towards Pseudomonas aeruginosa, it had no effect on bacterial growth. On the other hand, it showed a significant anti-biofilm activity. We provide evidence that OXYL can adhere to the surface of human cancer cell lines BT-474, MCF-7, and T47D, with no cytotoxic effect. In BT-474 cells, OXYL led to a moderate activation of the p38 kinase in the MAPK signaling pathway, without affecting the activity of caspase-3. Bacterial agglutination, anti-biofilm activity, cell adhesion, and p38 activation were all suppressed by co-presence of LacNAc. This is the first report on a type-2 LacNAc-specific lectin characterized by a C1q structural fold.

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Lectins as mitosis stimulating factors: Briefly reviewed

Cited by 32 publications

References 70 publications

Targeted disruption of pi–pi stacking in Malaysian banana lectin reduces mitogenicity while preserving antiviral activity

Targeted disruption of pi–pi stacking in Malaysian banana lectin reduces mitogenicity while preserving antiviral activity

The lectin ArtinM activates RBL-2H3 mast cells without inducing degranulation

Functional Characterization of OXYL, A SghC1qDC LacNAc-specific Lectin from The Crinoid Feather Star Anneissia Japonica

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