SUMOylation mediates the disassembly of the Smad4 nuclear export complex via RanGAP1 in KELOIDS

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.     

Pimelic Acid as a Degradation Product of Azelaic Acid by Yeasts

Ebp2p is essential for the assembly of 60S ribosomal subunits, and it interacts with other ribosome assembly factors in Saccharomyces cerevisiae. Two-hybrid screening exhibited that Ebp2p interacted with a small ubiquitin-related modifier (SUMO)-ligase Siz2p and SUMO-related proteins, Ris1p and Wss1p. Mutations of SUMO attachment sites of Ebp2p led to significantly weak interactions with Siz2p, Wss1p, and Ris1p, whereas they exhibited positive interactions with ribosome assembly factors. A SUMO-binding motif of Ris1p was required for interaction with Ebp2p. These results suggest that SUMO mediates the interaction between Ebp2p and SUMO related proteins and that Ebp2p switches its interaction partners via sumoylation.     

ATF3 and CH25H regulate effector trogocytosis and anti-tumor activities of endogenous and immunotherapeutic cytotoxic T lymphocytes

1. Download : Download high-res image (177KB)
2. Download : Download full-size image