Dr. Zhejian Ji received his bachelor’s degree from Tsinghua University in 2010. He then moved to the University of Texas Southwestern Medical Center for graduate study, where he work with Dr. Hongtao Yu and studied the mechanism of mitotic spindle checkpoint. In 2017, he started his postdoctoral research with Dr. Tom Rapoport at Harvard Medical School, studying function of a protein machine named Cdc48/p97 in protein degradation pathway. By far, Dr. Ji has published research papers on Science, Molecular Cell, and eLife as the first or co-first author. In the spring of 2023, Dr. Ji launched his own laboratory studying protein machines.

ATP is an essential energy currency in our cells, just like electricity to our home. We use a wide variety of electrical machines in our daily life. Similarly, our cells employ various protein machines named ATPases, which utilize energy from ATP hydrolysis to remodel their substrate molecules. The AAA-family ATPases are powerful nano-scale molecular machines that can remodel macromolecules, such as proteins and DNA. Their functions range from protein transport, degradation, to complex assembly and disassembly.

Based on their substrate spectra, the AAA-family ATPases can be divided into three categories – promiscuous type, specific type, and orphan type. The promiscuous ATPases function to promote unfolding and degradation of a wide variety of substrate proteins. They are therefore important regulators for protein homeostasis. Each of the specific-type ATPases, on the other hand, processes only a handful of substrates. Nevertheless, their ability to remodel substrate molecules renders them critical for certain biological pathways. In addition, the orphan-type ATPases act on substrates that are yet to be identified. The molecular mechanisms how these ATPases act on their substrates are far from understood. During his postdoc, Dr. Ji has revealed the mechanism of Cdc48/p97, a typical promiscuous-type ATPase, in processing ubiquitinated protein substrates. His work has highlighted the pivotal function of Cdc48/p97 in the ubiquitin-proteasome system, a major protein degradation pathway in cell. In future, the Ji lab aims to understand the functions of the specific- and orphan-type ATPases, by using a combination of biochemistry, structural biology, and cell biology approaches. Meanwhile, the lab also plans to develop nano-protein machines that are applicable for targeted protein degradation. Specific directions include:

(i) Regulation of cytoskeleton regulation and cell division

(ii) Assembly of nuclear pore complex

(iii) Nano-machines for targeted protein degradation

To learn more about the research, please visit https://zhejianji-lab.org/

(*co-first authors, #co-corresponding authors)

1. Zhejian Ji*#, Hao Li*, Daniele Peterle, Joao A. Paulo, Scott B. Ficarro, Thomas E. Wales, Jarrod A. Marto, Steven P. Gygi, John R. Engen, Tom A. Rapoport#. Translocation of polyubiquitinated protein substrates by the hexameric Cdc48 ATPase. (2022) Molecular Cell, 82(3):570-584. doi: 10.1016/j.molcel.2021.11.033.

2. Edward C. Twomey*, Zhejian Ji*, Thomas E. Wales, Nicholas O. Bodnar, Scott B. Ficarro, Jarrod A. Marto, John R. Engen, Tom A. Rapoport. Substrate processing by the Cdc48 ATPase complex is initiated by ubiquitin unfolding. (2019) Science, 365(6452):eaax1033. doi: 10.1126/science.aax1033.

3. Nicholas O. Bodnar, Kelly H. Kim, Zhejian Ji, Thomas E. Wales, Vladimir Svetlov, Evgeny Nudler, John R. Engen, Thomas Walz, Tom A. Rapoport. Structure of the Cdc48 ATPase with its ubiquitin-binding cofactor Ufd1-Npl4. (2018) Nature Structural and Molecular Biology, 25(7):616-622. doi: 10.1038/s41594-018-0085-x.

4. Zhejian Ji*, Haishan Gao*, Luying Jia, Bing Li, Hongtao Yu. A sequential multi-target Mps1 phosphorylation cascade promotes spindle checkpoint signaling. (2017) eLife, 6:e22513. doi: 10.7554/eLife.22513.

5. Zhejian Ji, Haishan Gao, Hongtao Yu. Kinetochore attachment sensed by competitive Mps1 and microtubule binding to Ndc80C. (2015) Science, 348(6240):1260–1264. doi: 10.1126/science.aaa4029.

jizhejian@westlake.edu.cn

We are interested in understanding the molecular mechanisms of different protein machines inside the cell. We are looking for dedicated postdocs, students, and staffs to join the forces. For more information, please visit: https://zhejianji-lab.org/