Abstract
Ubiquitination is known as important post-translational modification in cancer-related pathways. Human deubiquitinases (DUBs), with functions of modulating the ubiquitination process, are a family with about 100 proteins. They mainly function by cutting ubiquitin chains of the substrates. The Machado-Joseph domain-containing proteases (MJDs) is one of the sub-families of DUBs, consisting of four members, namely, Ataxin-3, Ataxin-3L, JOSD1, and JOSD2. Recent studies have provided new insights into biological functions of MJDs in the progression of Machado-Joseph disease or cancer diseases. In this review, we summarized the cellular functions and regulatory mechanisms of MJDs in Machado-Joseph disease and cancer pathways. Furthermore, we summarized MJDs genetic alterations in different human cancers by exploring the public databases (cBioportal). The aim of this review is to provide a comprehensive account based on our current knowledge about emerging insights into MJDs in physiology and disease, which might shed light on fundamental biological questions and promise to provide a potential target for therapeutic intervention.
Highlights
During deubiquitination process, with the help of deubiquitinases (DUBs), ubiquitinated proteins can cut ubiquitins of ubiquitinlinked protein substrates and reverse the process (Amerik and Hochstrasser, 2004)
As a family member of Machado-Joseph domaincontaining proteases (MJDs), Ataxin-3 has been well characterized to be involved in the progression of Machado-Joseph disease
The rest family members such as Ataxin-3L, JOSD1, and JOSD2 have been identified to be associated with tumor progression recently
Summary
With the help of deubiquitinases (DUBs), ubiquitinated proteins can cut ubiquitins of ubiquitinlinked protein substrates and reverse the process (Amerik and Hochstrasser, 2004). It is estimated to have around 100 DUBs in human cells, consisting of seven families, including ovarian tumor proteases (OTUs), ubiquitin carboxy-terminal hydrolases (UCHs), ubiquitin-specific proteases (USPs), Machado-Joseph domaincontaining proteases (MJDs), JAMM/MPN domain-associated metallopeptidases (JAMMs), monocyte chemotactic proteininduced protein (MCPIP), and Zinc finger with UFM1-specific peptidase domain protein (ZUFSP). MJDs is the smallest family of the DUBs. All MJD family members have a common cysteine protease domain, namely Josephin domain (Figure 1), consisting of around 180 amino acids. Homologs of Josephin proteins, which can be found in plants and protozoans, are widely distributed among metazoans. This highly conserved domain implies important roles of the MJD family members, in most cases, their biological functions remain largely unanswered. We focus on increasingly recognized involvement of MJDs in human cancers and further discuss new findings revolving the prospect of MJDs as a target in human cancer therapy
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
