A study lead by Professor JIAO Renjie at IBP reports for the first time a link between the SUMO pathway and the JNK pathway through HIPK. This work provides a new model for further functional investigations of SUMO and for studying how JNK is regulated. It was accepted for publication in the Development magazine on March 23.

SUMO is a small molecule that is similar in its structure to ubiquitin, and the SUMOylation process resembles that of ubiquitination as well. However, the results of these two processes are largely different with ubiquitination often mediates protein degradation, while SUMOylation functionally regulates its target proteins. SUMO has been shown to be involved in the regulation of gene transcription, DNA repair and genome stability, ion channel function, biological rhythms and so on. Alterations of the JNK pathway may lead to heart disease, diabetes, apoptosis and multiple kinds of human cancers, thus JNK is a potential target for molecular therapies.

Drosophila is an excellent model system for studying the biological functions of SUMOylation because only one single gene, smt3, in the Drosophila genome encodes the SUMO molecule. Loss of function of smt3 leads to embryonic lethality due to that fact that SUMO is required for multiple biological processes. Huang et al. in Jiao lab using powerful molecular genetic tools specifically knocked down the function of smt3 in various tissues, which led to developmental arrests of these tissues such as the eye, the wing and the notum (Fig. 1).

Fig. 1. Specific knockdown of smt3 leads to developmental arrests A, B, and C show wild type eye, wing and notum respectively while in A’, B’ and C’ are the aberrant eye, wing or notum after knockdown of smt3 gene.

Further cellular and biochemical studies demonstrate that knockdown of smt3 lead to the translocation of unsumoylated Hipk from the nucleus to the cytoplasm, where it activates the JNK pathway, causing the developmental arrests of the corresponding tissues.