Fig 8.

A model in which VEGF promotes HDAC7 phosphorylation and FLNB ubiquitination to promote HDAC7 cytoplasmic sequestration. Subcellular distribution of HDAC7 is controlled by an N-terminal nuclear localization sequence (NLS) and a C-terminal nuclear export sequence (NES). CRM1 recognizes NES and promotes HDAC7 nuclear export, and importin binds the NLS and promotes HDAC7 nuclear localization (20). VEGF-A binds and induces activation of VEGFR2 downstream kinases including PKC and PKD. Activated PKD phosphorylates HDAC7 to generate 14-3-3 binding sites (9, 10), whereas activated PKC promotes ubiquitination of FLNB, which binds and masks the HDAC7 NLS from importin binding, thus blocking HDAC7 from nuclear entry.