Cell Cycle Regulation by Carboxylated Multiwalled Carbon Nanotubes through p53-Independent Induction of p21 under the Control of the BMP Signaling Pathway

This report describes how carboxylated multiwalled carbon nanotubes (MWCNTs) induce p53-independent p21 expression and cell cycle arrest. MWCNTs suppress BMP signaling and lead to the downregulation of Id protein production and the upregulation of p21 because p21 expression is directly controlled by Id proteins through their regulation of the E-box motifs in the p21 promoter. The overexpressed p21 protein then binds to the cyclin D/cdk4,6 complexes and inhibits the phosphorylation of Rb protein. Hypophosphorylation of Rb prevents the release of E2F factors and causes cell cycle arrest. These findings provide valuable insight into a mechanistic understanding of carbon nanotubes' effects on cellular functions.