A team led by Dr. Ruey-Hwa Chen, a Distinguished Research Fellow at the Institute of Biological Chemistry recently discovered that lysine (K) 33-linked ubiquitin chains function in protein trafficking. Ubiquitin is a small molecule that is 76 amino acids in length. Polyubiquitination is the attachment of a chain of ubiquitin molecules to a protein. Among the amino acids that make up ubiquitin seven lysines – K6, K11, K27, K29, K33, K48, and K63 – and the methionine (M1) may serve as points of ubiquitination. Scientists understand the functions of the K48- and K63-linked ubiquitin chains reasonably well, but the functions of the chains that form at the other lysines remained unknown. The discovery of the function of K33-linked ubiquitin chain in cells advances understanding in this field. The research was published in the top molecular and cell biology journal Molecular Cell on April 24, 2014.

         In the study, the scientists found that an enzyme named Cullin3 ubiquitin E3 ligase which contains KLHL20 as the receptor of the substrate can catalyze K33-linked ubiquitination on a protein named coronin 7 (Crn7). Crn is known to regulate actin, the protein that forms microfilaments that make up a large part of the cytoskeleton (scaffolding) of the cell. This atypical ubiquitin chain connects Crn7 to a ubiquitin-binding protein named Eps15 that is localized in the cellular organelle named the Golgi apparatus. This connection enables actin assembly at the Golgi apparatus that promotes transport of cell materials out of the Golgi apparatus (termed post-Golgi transport) through vesicles. Since post-Golgi transport in the cell is essential for many physiological processes, such as hormone secretion, immune responses, and neural transmission, the study also provides new insights into these important processes.

         "This study demonstrates, for the first time, how cells read the K33-linked ubiquitin chain," Dr. Chen commented.

         In 2012, the journal Molecular Cell had an impact factor of 15.280. The full article entitled "K33-linked polyubiquitination of coronin 7 by Cul3-KLHL20 ubiquitin E3 ligase regulates protein trafficking" can be found at the Molecular Cell website at: http://www.sciencedirect.com/science/article/pii/S1097276514002688  

         The full list of authors is: Wei-Chien Yuan, Yu-Ru Lee, Shu-Yu Lin, Li-Ying Chang, Yen Pei Tan, Chin-Chun Hung, Jean-Cheng Kuo, Cheng-Hsin Liu, Mei-Yao Lin, Ming Xu, Zhijian J. Chen, and Ruey-Hwa Chen. This research was financially supported by the Ministry of Science and Technology, Taiwan and Academia Sinica.