{Reference Type}: Journal Article
{Title}: SUMOylation mediates the disassembly of the Smad4 nuclear export complex via RanGAP1 in KELOIDS.
{Author}: Lin X;Pang Q;Hu J;Sun J;Dai S;Yu Y;Xu J;
{Journal}: J Cell Mol Med
{Volume}: 27
{Issue}: 8
{Year}: 04 2023
{Factor}: 5.295
{DOI}: 10.1111/jcmm.17216
{Abstract}: Sentrin/small ubiquitin-like modifier (SUMO) has emerged as a powerful mediator regulating biological processes and participating in pathophysiological processes that cause human diseases, such as cancer, myocardial fibrosis and neurological disorders. Sumoylation has been shown to play a positive regulatory role in keloids. However, the sumoylation mechanism in keloids remains understudied. We proposed that sumoylation regulates keloids via a complex. RanGAP1 acted as a synergistic, functional partner of SUMOs in keloids. Nuclear accumulation of Smad4, a TGF-β/Smad pathway member, was associated with RanGAP1 after SUMO1 inhibition. RanGAP1*SUMO1 mediated the nuclear accumulation of Smad4 due to its impact on nuclear export and reduction in the dissociation of Smad4 and CRM1. We clarified a novel mechanism of positive regulation of sumoylation in keloids and demonstrated the function of sumoylation in Smad4 nuclear export. The NPC-associated RanGAP1*SUMO1 complex functions as a disassembly machine for the export receptor CRM1 and Smad4. Our research provides new perspectives for the mechanisms of keloids and nucleocytoplasmic transport.