%A Wang,Faliang %A Zhu,Cuige %A Cai,Shirong %A Boudreau,Aaron %A Kim,Sun-Joong %A Bissell,Mina %A Shao,Jieya %D 2021 %J Frontiers in Cell and Developmental Biology %C %F %G English %K profilin-1 (Pfn1),Phosphorylation,Actin,poly-L-proline (PLP),Apoptosis,breast cancer,chemotherapy,Protein kinase A (PKA) %Q %R 10.3389/fcell.2021.692269 %W %L %M %P %7 %8 2021-June-21 %9 Original Research %# %! Ser71 phosphorylation of Pfn1 %* %< %T Ser71 Phosphorylation Inhibits Actin-Binding of Profilin-1 and Its Apoptosis-Sensitizing Activity %U https://www.frontiersin.org/articles/10.3389/fcell.2021.692269 %V 9 %0 JOURNAL ARTICLE %@ 2296-634X %X The essential actin-binding factor profilin-1 (Pfn1) is a non-classical tumor suppressor with the abilities toboth inhibit cellular proliferation and augment chemotherapy-induced apoptosis. Besides actin, Pfn1 interacts with proteins harboring the poly-L-proline (PLP) motifs. Our recent work demonstrated that both nuclear localization and PLP-binding are required for tumor growth inhibition by Pfn1, and this is at least partially due to Pfn1 association with the PLP-containing ENL protein in the Super Elongation Complex (SEC) and the transcriptional inhibition of pro-cancer genes. In this paper, by identifying a phosphorylation event of Pfn1 at Ser71 capable of inhibiting its actin-binding and nuclear export, we provide in vitro and in vivo evidence that chemotherapy-induced apoptotic sensitization by Pfn1 requires its cytoplasmic localization and actin-binding. With regard to tumor growth inhibition byPfn1, our data indicate a requirement for dynamic actin association and dissociation rendered by reversible Ser71phosphorylation and dephosphorylation. Furthermore, genetic and pharmacological experiments showed that Ser71 of Pfn1 can be phosphorylated by protein kinase A (PKA). Taken together, our data provide novel mechanistic insights into the multifaceted anticancer activities of Pfn1 and how they are spatially-defined in the cell and differentially regulated by ligand-binding.