How Proteasomes Make Decision for Complete or Partial Degradation

Proteins that are modified by a small ubiquitin to form ubiquitin chains are dedicated to proteasomes for degradation. Most of proteins undergo complete degradation, while a small group of proteins are degraded partially by proteasomes to form truncated functional products. Recently, researchers from Chinese Academy of Sciences reveal that Ter94/p97 ATPase and K11-linked ubiquitin chains play an important role in partial proteasomal degradation.

Hedgehog signaling plays important roles in metazoan development, and its malfunction is implicated in numerous human congenital disorders and cancers. The activity of Hedgehog signaling is transduced by Ci/Gli proteins, which can be either degraded completely or partially from a full-length active form to a truncated repressor by proteasomes. The mechanism of how proteasomes make decision for complete or partial degradation of Ci/Gli is poorly understood.

To answer this question, Dr. ZHAO Yun and his colleagues have investigated the partial/complete degradation of Ci in Drosophila. By using immunostaining and genetic assay, they found that Ter94 specifically regulates the partial degradation of Ci. They carried out a serial of biochemistry and cell based assay to further reveal that K11-linked ubiquitin chains only involved in Ci partial degradation. Finally, they presented evidence that Ter94 targets K11-linked ubiquitinated Ci to proteasomes for partial degradation. A conserved mechanism in mammals was shown that p97 also regulates the partial degradation of Gli3, which may shed light on a new design for medical intervention.

This work entitled ‘Ter94 ATPase Complex Targets K11-Linked Ubiquitinated Ci to Proteasomes for Partial Degradation’ was published online in Developmental Cell on June, 2013. And it’s conducted by Dr. ZHAO Yun, Dr. ZHANG Lei and their research teams from Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, in collaboration with Dr. Chi-chung Hui from University of Toronto.

This work was supported by research grants from Ministry of Science and Technology of China, National Natural Science Foundation of China, and Chinese Academy of Sciences.

Ter94 and K11-linked ubiquitin chains drive partial degradation of Ci (Image by Dr. ZHAO Yun’s group)