Fusicoccin is a diterpene glycoside phytotoxin extracted from the fungus Phomopsis amygdaliand. Fusicoccin a stabilizer of 14-3-3 protein interactions. Fusicoccin activates the plasma membrane H⁺-ATPase by stabilizing its binding to 14-3-3 proteins, leading to proton efflux and membrane hyperpolarization. Fusicoccin regulates multiple cellular signaling pathways by stabilizing the interactions between 14-3-3 proteins and client proteins containing a C-terminal recognition motif, such as ERα, GPIbα, TASK3, CFTR, and p53. Fusicoccin can be used in research related to plant physiology, cancer therapy, and neural regeneration[1-4].
In vitro, HEK293T cells were treated with Fusicoccin (5μM) for 60–90 minutes. Fusicoccin induced nuclear export of mCherry-CT52M1 and nuclear import of mCherry-p65-CT52M1. By stabilizing the interaction between 14-3-3 proteins and CT52M1, Fusicoccin regulated the subcellular localization of NF-κB and induced IL-8 secretion[5]. OVCAR-3 cells were co-treated with Fusicoccin (30μM) and IFNα (200U/mL) for 6 days. Fusicoccin A and IFNα synergistically reduced cell viability and induced apoptosis[6].
In vivo, adult mice with spinal cord contusion and T10 hemisection models were intraperitoneally administered Fusicoccin (15mg/kg; every other day) for 42 days. Fusicoccin promoted motor function recovery and neural regeneration[7]. Fusicoccin (5mg/kg; every two days) was administered intraperitoneally to Alzheimer's disease model C57BL6JRccHsd mice for 12 days. Fusicoccin protected the cell bodies of dopaminergic neurons in the substantia nigr[8].
References:
[1] Camoni L, Visconti S, Aducci P. The phytotoxin fusicoccin, a selective stabilizer of 14-3-3 interactions? IUBMB Life. 2013 Jun;65(6):513-7.
[2] Doveston RG, Kuusk A, Andrei SA, et al. Small-molecule stabilization of the p53 - 14-3-3 protein-protein interaction. FEBS Lett. 2017 Aug;591(16):2449-2457.
[3] Kaplan A, Morquette B, Kroner A, et al. Small-Molecule Stabilization of 14-3-3 Protein-Protein Interactions Stimulates Axon Regeneration. Neuron. 2017 Mar 8;93(5):1082-1093.e5.
[4] Bury M, Andolfi A, Rogister B, et al. Fusicoccin a, a phytotoxic carbotricyclic diterpene glucoside of fungal origin, reduces proliferation and invasion of glioblastoma cells by targeting multiple tyrosine kinases. Transl Oncol. 2013 Apr;6(2):112-23.
[5] Skwarczynska M, Molzan M, Ottmann C. Activation of NF-κB signalling by fusicoccin-induced dimerization. Proc Natl Acad Sci U S A. 2013 Jan 29;110(5):E377-86.
[6] Andlovic B, Heilmann G, Ninck S, et al. IFNα primes cancer cells for Fusicoccin-induced cell death via 14-3-3 PPI stabilization. Cell Chem Biol. 2023 Jun 15;30(6):573-590.e6.
[7] Liu Q, Yang H, Luo J, et al. 14-3-3 protein augments the protein stability of phosphorylated spastin and promotes the recovery of spinal cord injury through its agonist intervention. Elife. 2024 Jan 17;12:RP90184.
[8] Vinueza-Gavilanes R, Bravo-González JJ, Basurco L, et al. Stabilization of 14-3-3 protein-protein interactions with Fusicoccin-A decreases alpha-synuclein dependent cell-autonomous death in neuronal and mouse models. Neurobiol Dis. 2023 Jul;183:106166.