CNOT1 is involved in TTP-mediated ICAM-1 and IL-8 mRNA decay

Abstract

Subunit 1 is the scaffold protein of the carbon catabolite repressor protein 4 (CCR4)-negative on TATA (NOT) complex (CNOT1). In our previous study, it was reported that tristetraprolin (TTP) could recruit subunit 7 of the CCR4-NOT complex (CNOT7) to induce the degradation of intercellular adhesion molecule-1 (ICAM-1) and interleukin-8 (IL-8) mRNA in human pulmonary microvascular endothelial cells (HPMECs). It was additionally demonstrated that TTP, CNOT7 and CNOT1 formed a complex in HPMECs. However, whether CNOT1 is involved in TTP-mediated ICAM-1 and IL-8 mRNA decay remains unclear. The present study demonstrated that CNOT1 knockdown improved ICAM-1 and IL-8 mRNA stabilization and protein expression levels. The immunofluorescence results demonstrated that CNOT1, CNOT7 and TTP are co-localized in the cytoplasm. CNOT1 silencing abolished CNOT7 and TTP coimmunoprecipitation. However, CNOT7 silencing did not influence CNOT1 and TTP coimmunoprecipitation, and TTP silencing additionally did not influence CNOT1 and CNOT7 coimmunoprecipitation. These results together with the authors' previous study, have identified that CNOT1 provides a platform for the recruitment of TTP and CNOT7, and is involved in TTP-mediated ICAM-1 and IL-8 mRNA decay.