Galectin‐4 is involved in p27‐mediated activation of the myelin basic protein promoter

Abstract

Our previous studies have found that expression of p27 in oligodendrocytes enhances myelin basic protein (MBP) gene expression through a mechanism that involves the transcription factor Sp1. In this study we show that this activation only requires the N-terminal 45 amino acids of p27 containing a functional cyclin-binding motif. In an effort to identify other cofactors that are involved in the p27-mediated activation of MBP gene expression, a yeast two-hybrid assay was performed using an N-terminal truncated p27 and a mouse embryo cDNA library. Galectin-4 was found to interact with p27 in the yeast two-hybrid assay. This novel interaction was also confirmed using a glutathione-S-transferase interaction assay and immunoprecipitation assays. Expression of galectin-4 in primary oligodendrocytes was confirmed by western blot. Additionally, the MBP promoter could be activated by expression of galectin-4 in CG4 oligodendrocytes, similar to the effects of increased p27 levels. We also show that Sp1 and galectin-4 interact in cells, while a complex of all three proteins could not be found. We conclude that galectin-4 is involved in the p27-mediated activation of the MBP gene, possibly through modulation of the glycosylation status of the transcription factor Sp1.

Galectin-4 expression is associated with reduced lymph node metastasis and modulation of Wnt/β-catenin signalling in pancreatic adenocarcinoma

“…Possibly, Gal-4 cross-links these components, thereby stabilizing the destruction complex, and enhancing degradation of β-cat. Furthermore, Gal-4 is shown to inhibit the IL-6/NF-kB/STAT3 pathway [11], to induce expression of the Wnt signaling inhibitor protein Naked1, and is involved in maintaining p27 levels in CRC [15, 43, 44]. Collectively, these effects due to involvement of Gal-4 might contribute to reduced cell migration.…”

Interweaving the Cell Cycle Machinery with Cell Differentiation

“…Progression of these cells into mature oligodendrocytes requires p21, 40 which may inhibit residual cdk4 kinase activity. Furthermore, p27 and p57 have been shown to directly control expression of myelin basic protein through CDK-independent (p27 45 ) and CDK-dependent mechanisms (p57 46 ). Lengner system takes advantage of the fact that mesenchymal mouse embryo fibroblasts grown in micromass can be induced to enter the chondrogenic lineage following treatment with BMP2.…”

“…p27, through its interaction with Galectin-4 and stabilization of Sp1, has been implicated in the activation of the myelin basic protein (MBP) promoter. 45 The related cdk inhibitor p57 is also required both for initiating cell cycle exit, and later for expression of myelin. 46 Although it is exciting to think of cdk inhibitors carrying out differentiation-promoting functions independently of their ability to regulate cdk activity and cell cycle exit, it is important to note that regulating cell proliferation is not necessarily the same as regulating cdk activity.…”

"Time sweet time": circadian characterization of galectin-1 null mice

“…Moreover, Gal1 expression in glial cells [28,29,40,41] provides an additional substrate for immune-related effects on circadian responses, since glial cells have been implicated in the generation and modulation of circadian rhythms [16,42]. In particular, astrocytic-derived Gal1 has also been reported to modulate glutamate neurotoxicity by altering the expression of NMDA receptors [31], which are key actors in the signal transduction pathway for circadian responses to light [43].…”