The Complex of p-Tyr42 RhoA and p-p65/RelA in Response to LPS Regulates the Expression of Phosphoglycerate Kinase 1

Inflammation plays a crucial role in tumorigenesis, primarily mediated by NF-kappa B. RhoA GTPases are instrumental in regulating the activation of NF-kappa B. Specifically, the phosphorylation of Tyrosine 42 on RhoA ensures the activation of NF-kappa B by directly activating the IKK beta associated with IKK gamma (NEMO). This study aimed to uncover the molecular mechanism through which p-Tyrosine 42 RhoA, in conjunction with NF-kappa B, promotes tumorigenesis. Notably, we observed that p-Tyrosine 42 RhoA co-immunoprecipitated with the p-Ser 536 p65/RelA subunit in NF-kappa B in response to LPS. Moreover, both p-Tyrosine 42 RhoA and p-p65/RelA translocated to the nucleus, where they formed a protein complex associated with the promoter of phosphoglycerate kinase 1 (PGK1) and regulated the expression of PGK1. In addition, p-p65/RelA and p-Tyr42 RhoA co-immunoprecipitated with p300 histone acetyltransferase. Intriguingly, PGK1 exhibited an interaction with beta-catenin, PKM1 and PKM2. Of particular interest, si-PGK1 led to a reduction in the levels of beta-catenin and phosphorylated pyruvate dehydrogenase A1 (p-PDHA1). We also found that PGK1 phosphorylated beta-catenin at the Thr551 and Ser552 residues. These findings discovered that PGK1 may play a role in transcriptional regulation, alongside other transcription factors.