Open AccessTight junction protein ZO-2 modulates the nuclear accumulation of transcription factor TEAD
Author(s) -
Helios Gallego-Gutiérrez,
Laura González-González,
Leticia Ramírez-Martínez,
Esther López-Bayghen,
Lorenza GonzálezMariscal
Publication year - 2021
Publication title -
molecular biology of the cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.463
H-Index - 225
eISSN - 1939-4586
pISSN - 1059-1524
DOI - 10.1091/mbc.e20-07-0470
Subject(s) - biology , transcription factor , microbiology and biotechnology , dna binding protein , transcription (linguistics) , nuclear protein , genetics , gene , linguistics , philosophy
The presence of tight junction protein z onula o ccludens 2 (ZO-2) at the nucleus inhibits the transcription of genes regulated by TEAD transcription factor. Here, we analyzed whether the movement of ZO-2 into the nucleus modulates the nuclear concentration of TEAD. In sparse cultures of ZO-2 knockdown Madin-Darby canine kidney cells, nuclear TEAD was diminished, as in parental cells transfected with a ZO-2 construct without nuclear localization signals, indicating that ZO-2 facilitates the entry of TEAD into the nucleus. Inhibition of nPKCδ in parental cells triggers the interaction between ZO-2 and TEAD at the cytoplasm and facilitates TEAD/ZO-2 complex nuclear importation. Using proximity ligation, immunoprecipitation, and pull-down assays, TEAD/ZO-2 interaction was confirmed. Nuclear TEAD is phosphorylated, and its exit in parental cells is enhanced by activation of a ZO-2 nuclear exportation signal by nPKCε, while the nuclear accumulation of ZO-2 triggered by the mutation of ZO-2 nuclear export signals induces no change in TEAD nuclear concentration. In summary, our results indicate that the movements of ZO-2 in and out of the nucleus modulate the intracellular traffic of TEAD through a process regulated by nPKCδ and ε and provide a novel role of ZO-2 as a nuclear translocator of TEAD.