O-GlcNAc transferase regulates p21 protein levels and cell proliferation through the FoxM1-Skp2 axis in a p53-independent manner.

ABSTRACT: The protein product of the CDKN1A gene, p21, has been extensively characterized as a negative regulator of the cell cycle. Nevertheless, it is clear that p21 has manifold complex and context-dependent roles that can be either tumor suppressive or oncogenic. Most well studied as a transcriptional target of the p53 tumor suppressor protein, there are other means by which p21 levels can be regulated. In this study, we show that pharmacological inhibition or siRNA-mediated reduction of O-GlcNAc transferase (OGT), the enzyme responsible for glycosylation of intracellular proteins, increases expression of p21 in both p53-dependent and p53-independent manners in nontransformed and cancer cells. In cells harboring WT p53, we demonstrate that inhibition of OGT leads to p53-mediated transactivation

SUBMITTER: de Queiroz RM 

PROVIDER: S-EPMC9418910 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature