Unknown

Dataset Information

0

Hyper-O-GlcNAcylation activates nuclear factor ?-light-chain-enhancer of activated B cells (NF-?B) signaling through interplay with phosphorylation and acetylation.


ABSTRACT: O-GlcNAcylation is the covalent addition of an O-linked ?-N-acetylglucosamine (O-GlcNAc) sugar moiety to hydroxyl groups of serine/threonine residues of cytosolic and nuclear proteins. O-GlcNAcylation, analogous to phosphorylation, plays critical roles in gene expression through direct modification of transcription factors, such as NF-?B. Aberrantly increased NF-?B O-GlcNAcylation has been linked to NF-?B constitutive activation and cancer development. Therefore, it is of a great biological and clinical significance to dissect the molecular mechanisms that tune NF-?B activity. Recently, we and others have shown that O-GlcNAcylation affects the phosphorylation and acetylation of NF-?B subunit p65/RelA. However, the mechanism of how O-GlcNAcylation activates NF-?B signaling through phosphorylation and acetylation is not fully understood. In this study, we mapped O-GlcNAcylation sites of p65 at Thr-305, Ser-319, Ser-337, Thr-352, and Ser-374. O-GlcNAcylation of p65 at Thr-305 and Ser-319 increased CREB-binding protein (CBP)/p300-dependent activating acetylation of p65 at Lys-310, contributing to NF-?B transcriptional activation. Moreover, elevation of O-GlcNAcylation by overexpression of OGT increased the expression of p300, IKK?, and IKK? and promoted IKK-mediated activating phosphorylation of p65 at Ser-536, contributing to NF-?B activation. In addition, we also identified phosphorylation of p65 at Thr-308, which might impair the O-GlcNAcylation of p65 at Thr-305. These results indicate mechanisms through which both non-pathological and oncogenic O-GlcNAcylation regulate NF-?B signaling through interplay with phosphorylation and acetylation.

SUBMITTER: Ma Z 

PROVIDER: S-EPMC5454098 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

altmetric image

Publications

Hyper-<i>O</i>-GlcNAcylation activates nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) signaling through interplay with phosphorylation and acetylation.

Ma Zhiyuan Z   Chalkley Robert J RJ   Vosseller Keith K  

The Journal of biological chemistry 20170417 22


<i>O</i>-GlcNAcylation is the covalent addition of an <i>O</i>-linked β-<i>N</i>-acetylglucosamine (<i>O</i>-GlcNAc) sugar moiety to hydroxyl groups of serine/threonine residues of cytosolic and nuclear proteins. <i>O</i>-GlcNAcylation, analogous to phosphorylation, plays critical roles in gene expression through direct modification of transcription factors, such as NF-κB. Aberrantly increased NF-κB <i>O</i>-GlcNAcylation has been linked to NF-κB constitutive activation and cancer development. T  ...[more]

Similar Datasets

| S-EPMC3469781 | biostudies-literature
| S-EPMC1234328 | biostudies-literature
| S-EPMC2099237 | biostudies-literature
| S-EPMC3663532 | biostudies-literature
| S-EPMC3330162 | biostudies-literature
| S-EPMC6218406 | biostudies-other
| S-EPMC6598431 | biostudies-literature
| S-EPMC4999498 | biostudies-literature
| S-EPMC5336175 | biostudies-literature
2019-06-07 | GSE114551 | GEO