Non-Traditional Roles of Protein Ubiquitination in Cellular Processes and Health

Dear Colleagues,

Protein ubiquitination is one of the most common post-translational modifications and is achieved via the covalent conjugation of the 76-amino-acid ubiquitin polypeptide on lysine (K) residues of substrates, a process governed by sequential catalyzation by the ubiquitin-activating enzyme (E1), the conjugating enzyme (E2), and ligase (E3). These enzymes also promote the formation of polyubiquitin chains linked with one of seven lysine residues (K6, K11, K27, K29, K33, K48, and K63) or the first methionine (M1) of ubiquitin, resulting in at least eight chain linkages. Ubiquitin modification in a protein is widely known as the primary mechanism of protein turnover executed via proteasomal degradation in the cell, and this is seen as the “traditional” function of polyubiquitin tagging and is usually K48-linked. Since its initial discovery through studies on NF-kB signaling, the non-proteasome-targeting roles of protein polyubiquitination have also been recognized, and the relevant knowledge has been rapidly growing. A concomitantly accepted concept is the complexity of ubiquitin chain topologies. As well as mono-ubiquitin modification and homotypic chain formation, heterotypic ubiquitin chains that are mixed or branched have been documented. Consequently, different ubiquitin chain topologies are associated with distinct modulations in protein functions. The specific codes embodied in distinct ubiquitin chain architectures are deciphered by “readers”, which bind ubiquitin-modified proteins to translate the signals into different functional outputs. Nonproteolytic ubiquitin signaling is finely orchestrated and tightly regulated within the cell, with the “eraser” function of deubiquitinases providing a counterbalance. The dysregulation of non-traditional ubiquitin code writers, readers, and erasers has been linked to diverse human diseases, including immunodeficiency, neurodegenerative diseases, and cancer. Additionally, non-traditional ubiquitination can be utilized by microbial virulence factors to induce pathogenesis and/or host immune response. Emerging studies suggest that key components in non-traditional ubiquitin signaling pathways may represent viable therapeutic targets in the treatment of a variety of pathologic conditions.

This Special Issue will showcase a collection of original research and review articles addressing non-traditional functions of protein ubiquitination and their underlying molecular and cellular mechanisms. We welcome studies that report new findings on functional roles, ubiquitin chain coding, decoding and erasing processes, and disease association in non-traditional protein ubiquitination, as well as structural and other investigations that aid in understanding the dysregulated mechanisms underlying diseases and the design of therapeutic targeting strategies. Manuscript submissions reporting technical advances in analyzing ubiquitin chain topologies are also encouraged.

Dr. Chuanjin Wu
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cells is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

• Protein Ubiquitination;
• Ubiquitin chain;
• k63-linked ubiquitination;  
• linear ubiquitination;
• ubiquitin-binding proteins;
• deubiquitinases;
• NF-kB;
• autophagy;
• inflammation;
• immunodeficiency;
• neurodegenerative diseases.