Special Issue "Ubiquitin-Related Cancer"
A special issue of Cancers (ISSN 2072-6694).
Deadline for manuscript submissions: 1 September 2020.
Interests: ubiquitin-proteasome system; cancer pathogenesis
Knowledge of ubiquitin (Ub) has dramatically evolved from that of a molecular tag that directs proteasome degradation to that of an important cell-signaling molecule that orchestrates the activity of myriad cellular pathways. Ub modification serves important and at times essential roles in nearly all cellular events, with many at the center of the biology of cancer. Key roles in events that span the distance from the cell surface to the chromatin and back place Ub in a key position to influence many of the hallmarks of cancer. This notion becomes even more complex when one considers ubiquitin-like proteins (UbLs) and the increasing recognition of their roles in malignancy. Ongoing research has now uncovered roles for Ub and Ub(L) conjugating and deconjugating enzymes as oncogenes, non-oncogenes, and tumor suppressor genes. With the unraveling of the role of Ub and UbLs in cancer, there has been a growing interest in the development of small-molecule inhibitors targeting enzymes in these pathways to be used as novel anti-neoplastic agents.
The FDA and EMA approval and subsequent success of the first in class proteasome inhibitor bortezomib served as proof of principle that these pathways are important as cancer targets. The proteasome, of course, is only one component of the ubiquitin economy and targeting individual steps in the pathway may offer much greater specificity and efficacy. The enzymatic steps involved in the addition and removal of Ub(L)s to targets have been relatively well characterized. The addition side of the equation involves a three-step process involving activating enzymes (E1s), conjugating enzymes (E2s), and ligases (E3s). The deconjugation of Ub(Ls) is catalyzed by a set of enzymes that cleave the isopeptide bond (isopeptidases) between the Ub(L) and substrates. The E1, E2, some E3s, and most Ub(L) isopeptidases require an active-site cysteine, whereas some isopeptidases are metalloproteases.
Existing medications such as thalidomide and its derivatives that target the Ub E3 ligase cereblon have demonstrated the therapeutic potential of selective E3 ligase inhibition in cancer. New inhibitors of the conjugation of Ub and UbLs to cellular targets are under clinical development, with the NEDD8-activating enzyme inhibitor MLN4924 (Pevonedistat) involved in 34 clinical trials at various stages of enrollment and inhibitors for the ubiquitin and SUMO (small ubiquitin-like modifier) activating enzymes also in the pipeline. We are just beginning to develop and study the potential efficacy of Ub(L) isopeptidase inhibitors as potential therapeutics.
This Special Issue of Cancers on “Ubiquitin-Related Cancer” will cover the involvement of Ub(L)s and the enzymes involved in their attachment and removal to substrates in cancer development, progression, and therapy resistance, and as targets of therapy to consolidate and further stimulate work in these fields.
Dr. Paul Galardy
Manuscript Submission Information
Manuscripts should be submitted online at www.ynsqex.icu 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 papers will be 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. Cancers is an international peer-reviewed open access monthly 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 2200 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.
- E3 ligase
- E2 conjugating enzyme
- E1 activating enzyme
- Deubiquitinating enzyme