Galectin

About: Galectin is a research topic. Over the lifetime, 2076 publications have been published within this topic receiving 103409 citations. The topic is also known as: IPR001079 & Galectin.

Design of a peptidic inhibitor that targets the dimer interface of a prototypic galectin.

Abstract: // Maria Claudia Vladoiu 1 , Marilyne Labrie 1 , Myriam Letourneau 1 , Philippe Egesborg 1 , Donald Gagne 1 , Etienne Billard 1 , Andree-Anne Grosset 1 , Nicolas Doucet 1 , David Chatenet 1 , Yves St-Pierre 1 1 INRS-Institut Armand-Frappier, Universite du Quebec, Laval, Quebec, H7V 1B7 Canada Correspondence to: Yves St-Pierre, e-mail: yves.st-pierre@iaf.inrs.ca Keywords: galectin, inhibitor, peptide, apoptosis, T-cells Received: May 13, 2015 Accepted: August 20, 2015 Published: October 01, 2015 ABSTRACT Galectins are small soluble lectins that bind α-galactosides via their carbohydrate recognition domain (CRD). Their ability to dimerize is critical for the crosslinking of glycoprotein receptors and subsequent cellular signaling. This is particularly important in their immunomodulatory role via the induction of T-cell apoptosis. Because galectins play a central role in many pathologies, including cancer, they represent valuable therapeutic targets. At present, most inhibitors have been directed towards the CRD, a challenging task in terms of specificity given the high structural homology of the CRD among galectins. Such inhibitors are not effective at targeting CRD-independent functions of galectins. Here, we report a new class of galectin inhibitors that specifically binds human galectin-7 (hGal-7), disrupts the formation of homodimers, and inhibits the pro-apoptotic activity of hGal-7 on Jurkat T cells. In addition to representing a new means to achieve specificity when targeting galectins, such inhibitors provide a promising alternative to more conventional galectin inhibitors that target the CRD with soluble glycans or other small molecular weight allosteric inhibitors.

How altering the modular architecture affects aspects of lectin activity: case study on human galectin-1.

Abstract: Discoveries on involvement of glycan-protein recognition in many (patho)physiological processes are directing attention to exploring the significance of a fundamental structural aspect of sugar receptors beyond glycan specificity, i.e., occurrence of distinct types of modular architecture. In order to trace clues for defining design-functionality relationships in human lectins, a lectin's structural unit has been used as source material for engineering custom-made variants of the wild-type protein. Their availability facilitates comparative analysis toward the stated aim. With adhesion/growth-regulatory human galectin-1 as example, the strategy of evaluating how changes of its design (here, from the homodimer of non-covalently associated domains to (i) linker-connected di- and tetramers and (ii) a galectin-3-like protein) affect activity is illustrated by using three assay systems of increasing degree of glycan complexity. Whereas calorimetry with two cognate disaccharides and array testing with 647 (glyco)compounds disclosed no major changes, galectin histochemical staining profiles of tissue sections that present natural glycome complexity revealed differences between wild-type and linker-connected homo-oligomers as well as between the galectin-3-like variant and wild-type galectin-3 for cell-type positivity, level of intensity at the same site and susceptibility for inhibition by a bivalent glycocompound. These results underscore the strength of the documented approach. Moreover, they give direction to proceed to (i) extending its application to other members of this lectin family, especially galectin-3 and (ii) then analyzing impact of architectural alterations on cell surface lattice formation and ensuing biosignaling systematically, considering the variants' potential for translational medicine.

Human Cytomegalovirus Upregulates Expression of the Lectin Galectin 9 via Induction of Beta Interferon

Abstract: Regulation of the lectin galectin 9 (Gal-9) was investigated for the first time during human cytomegalovirus (HCMV) infection. Gal-9 transcription was significantly upregulated in transplant recipients with reactivated HCMV in vivo. In vitro, Gal-9 was potently upregulated by HCMV independently of viral gene expression, with interferon beta (IFN-β) identified as the mediator of this effect. This study defines an immunoregulatory protein potently increased by HCMV infection and a novel mechanism to control Gal-9 through IFN-β induction.

Galectin-12 in Cellular Differentiation, Apoptosis and Polarization.

Abstract: Galectin-12 is a member of a family of mammalian lectins characterized by their affinity for β-galactosides and consensus amino acid sequences. The protein structure consists of a single polypeptide chain containing two carbohydrate-recognition domains joined by a linker region. Galectin-12 is predominantly expressed in adipose tissue, but is also detected in macrophages and other leukocytes. Downregulation of galectin-12 in mouse 3T3-L1 cells impairs their differentiation into adipocytes. Conversely, overexpression of galectin-12 in vitro induces cell cycle arrest in G1 and apoptosis. Upregulation of galectin-12 and initiation of G1 cell cycle arrest are associated with driving pre-adipocytes toward terminal differentiation. Galectin-12 deficiency increases insulin sensitivity and glucose tolerance in obese animals. Galectin-12 inhibits macrophage polarization to the M2 population, enhancing inflammation and decreasing insulin sensitivity in adipocytes. Galectin-12 also affects myeloid differentiation, which is associated with chemotherapy resistance. In addition to highlighting the above-mentioned aspects, this review also discusses the potential clinical applications of modulating the function of galectin-12.