Coronin 1B is an actin-binding protein that plays important roles in actin-dependent cellular processes. We previously reported that coronin 1B is involved in vascular endothelial cell growth factor-induced migration of human umbilical vein endothelial cells (HUVECs). However, the role of coronin 1B in tumor necrosis factor alpha (TNF alpha)-induced endothelial cell apoptosis remained unknown. In this study, we investigated whether coronin 1B affects TNF alpha-induced HUVEC apoptosis and sought to elucidate the mechanism by which coronin 1B regulates this cellular process. Depletion of coronin 1B by siRNA transfection decreased TNF alpha-induced apoptosis of HUVECs, as determined by MIT, terminal deoxynucleotidyl transferase dUTP nick end labeling and caspase-3 activity assays. Coronin 1B depletion also decreased caspase-8 cleavage via a JNK-independent pathway. Coronin 1B interacted with Fas-associated death domain protein (FADD) in both a plasmid overexpression system in HEK293T cells and at the endogenous protein level in TNF alpha-stimulated HUVECs. Immunoprecipitation and in situ proximity ligation assays showed that coronin 1B depletion diminished the interaction between TNF alpha-induced TNF receptor-1-associated death domain protein (TRADD) and FADD, suggesting that coronin 1B is required for the TNF alpha-induced TRADD and FADD interaction and subsequent caspase-8/caspase-3 cascade activation, ultimately leading to apoptosis. (C) 2020 Published by Elsevier Inc.