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J Biol Chem. 2016 Jan 15;291(3):1529-37. doi: 10.1074/jbc.M115.672220. Epub 2015 Nov 20.

MicroRNA-424 Predicts a Role for β-1,4 Branched Glycosylation in Cell Cycle Progression.

Author information

1
From the Biomedical Chemistry Institute, Department of Chemistry, New York University, New York, New York 10003.
2
From the Biomedical Chemistry Institute, Department of Chemistry, New York University, New York, New York 10003 lkmahal@nyu.edu.

Abstract

MicroRNA regulation of protein expression plays an important role in mediating many cellular processes, from cell proliferation to cell death. The human microRNA miR-424 is up-regulated in response to anti-proliferative cytokines, such as transforming growth factor β (TGFβ), and directly represses cell cycle progression. Our laboratory recently established that microRNA can be used as a proxy to identify biological roles of glycosylation enzymes (glycogenes). Herein we identify MGAT4A, OGT, and GALNT13 as targets of miR-424. We demonstrate that MGAT4A, an N-acetylglucosaminyltransferase that installs the β-1,4 branch of N-glycans, is directly regulated by miR-424 in multiple mammary epithelial cell lines and observe the loss of MGAT4A in response to TGFβ, an inducer of miR-424. Knockdown of MGAT4A induces cell cycle arrest through decreasing CCND1 levels. MGAT4A does not affect levels of β-1,6 branched N-glycans, arguing that this effect is specific to β-1,4 branching and not due to gross changes in overall N-linked glycosylation. This work provides insight into the regulation of cell cycle progression by specific N-glycan branching patterns.

KEYWORDS:

CDC25A; Galectin-3; MGAT5; N-glycan biosynthesis; N-linked glycosylation; cell cycle; complex N-glycans; cyclin D1; glycosylation; microRNA (miRNA)

PMID:
26589799
PMCID:
PMC4714234
DOI:
10.1074/jbc.M115.672220
[Indexed for MEDLINE]
Free PMC Article

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