Sumoylation of Sp1 is increased by betulinic acid and led to RNF‐mediated degradation

Abstract

Our recent findings show that Sp1 can accumulate during tumorigenesis after it undergoes posttranslational modification, namely, sumoylation, and phosphorylation. We found that Sp1 was the substrate of the ubiquitin E3 ligase, RNF4. Mapping of the domain involved in the interaction between Sp1 and RNF4 revealed 2 regions that interacted with each other. One was a SUMO‐modifier in the N‐terminus of Sp1(Lys16) that interacted with the SUMO‐interacting motif (SIM) of RNF4, and the other was the C‐terminus of Sp1 that interacted with RNF4 in a SIM independent manner. We also found that a previous reported anticancer drug‐betulinic acid (BA) increases Sp1 sumoylation, facilitating interaction between Sp1 and RNF4, which leads to Sp1 degradation through the ubiquitin‐dependent proteasome pathway. Here, we elucidate that Sp1 degradation through BA treatment facilitate sumoylation of Sp1 during cancer therapies.