Progress in atypical ubiquitination via K6-linkages

Abstract

Ubiquitination is a post-translational modification of proteins in eukaryotes, which mediates the specific degradation and signal transduction of proteins to regulate a variety of life processes and thus affects functions of the body. The disorder and imbalance of ubiquitination network is a major cause of serious human diseases. Ubiquitin molecules can form eight homogeneous ubiquitin chains with different topological structures, which vary greatly in abundance and function. At present, the classical ubiquitin chains K48 and K63 with high abundance and rich substrates have been intensively studied, while other atypical ubiquitin chains with low content remain to be studied. However, it has been proved that atypical ubiquitin chains play a key role in intracellular regulation. K6 is an important atypical ubiquitin chain, which is similar to K48 chain and has a tight spatial structure. It plays a role in DNA damage repair, mitochondrial quality control, the occurrence and development of tumor, and the pathogenesis of Parkinson's disease. Due to the lack of specific antibodies and effective enrichment methods for K6, little is known about its substrate and regulatory mechanism. This paper systematically reviews the structural characteristics, regulatory mechanism, biological functions, and relevant diseases of atypical K6 linkages, aiming to provide reference for the functional study of K6.