For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
0
views
45
references
 Top references
cited by
0
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
0 collections
    0
    shares
      394
      similar
       All similar
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Ubiquitin: Not just a one‐way ticket to the proteasome, but a therapeutic dial to fine‐tune the molecular landscape of disease

      article-commentary

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Recently, there is a rise in studies that recognize the importance of targeting ubiquitin and related molecular machinery in various therapeutic contexts. Here we briefly discuss the history of ubiquitin, its biological roles in protein degradation and beyond, as well as the current state of ubiquitin‐targeting therapeutics across diseases. We conclude that targeting ubiquitin machinery is approaching a renaissance, and tapping its full potential will require embracing a wholistic perspective of ubiquitin's multifaceted roles.

          Related collections

          Most cited references45

          • Record: found
          • Abstract: found
          • Article: not found

          Protacs: chimeric molecules that target proteins to the Skp1-Cullin-F box complex for ubiquitination and degradation.

          K M Sakamoto, K. -B. Kim, A Kumagai … (2001)
          The intracellular levels of many proteins are regulated by ubiquitin-dependent proteolysis. One of the best-characterized enzymes that catalyzes the attachment of ubiquitin to proteins is a ubiquitin ligase complex, Skp1-Cullin-F box complex containing Hrt1 (SCF). We sought to artificially target a protein to the SCF complex for ubiquitination and degradation. To this end, we tested methionine aminopeptidase-2 (MetAP-2), which covalently binds the angiogenesis inhibitor ovalicin. A chimeric compound, protein-targeting chimeric molecule 1 (Protac-1), was synthesized to recruit MetAP-2 to SCF. One domain of Protac-1 contains the I kappa B alpha phosphopeptide that is recognized by the F-box protein beta-TRCP, whereas the other domain is composed of ovalicin. We show that MetAP-2 can be tethered to SCF(beta-TRCP), ubiquitinated, and degraded in a Protac-1-dependent manner. In the future, this approach may be useful for conditional inactivation of proteins, and for targeting disease-causing proteins for destruction.
          Article 0 comments Cited 656 times – based on 0 reviews     Review now
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Encoding and decoding cellular information through signaling dynamics.

            Jeremy E. Purvis, Galit Lahav (2013)
            A growing number of studies are revealing that cells can send and receive information by controlling the temporal behavior (dynamics) of their signaling molecules. In this Review, we discuss what is known about the dynamics of various signaling networks and their role in controlling cellular responses. We identify general principles that are emerging in the field, focusing specifically on how the identity and quantity of a stimulus is encoded in temporal patterns, how signaling dynamics influence cellular outcomes, and how specific dynamical patterns are both shaped and interpreted by the structure of molecular networks. We conclude by discussing potential functional roles for transmitting cellular information through the dynamics of signaling molecules and possible applications for the treatment of disease. Copyright © 2013 Elsevier Inc. All rights reserved.
            Article 0 comments Cited 313 times – based on 0 reviews     Review now
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              p53 dynamics control cell fate.

              Jeremy E. Purvis, Kyle Karhohs, Caroline Mock … (2012)
              Cells transmit information through molecular signals that often show complex dynamical patterns. The dynamic behavior of the tumor suppressor p53 varies depending on the stimulus; in response to double-strand DNA breaks, it shows a series of repeated pulses. Using a computational model, we identified a sequence of precisely timed drug additions that alter p53 pulses to instead produce a sustained p53 response. This leads to the expression of a different set of downstream genes and also alters cell fate: Cells that experience p53 pulses recover from DNA damage, whereas cells exposed to sustained p53 signaling frequently undergo senescence. Our results show that protein dynamics can be an important part of a signal, directly influencing cellular fate decisions.
              Article 0 comments Cited 311 times – based on 0 reviews     Review now
                Bookmark
                All references

                Author and article information

                Contributors
                Robin E. C. Lee:
                ORCID: https://orcid.org/0000-0001-7209-3929
                RobinLee@pitt.edu
                Journal
                Journal ID (nlm-ta): Clin Transl Med
                Journal ID (iso-abbrev): Clin Transl Med
                Journal ID (doi): 10.1002/(ISSN)2001-1326
                Journal ID (publisher-id): CTM2
                Title: Clinical and Translational Medicine
                Publisher: John Wiley and Sons Inc. (Hoboken )
                ISSN (Electronic): 2001-1326
                Publication date (Electronic): 17 July 2024
                Publication date Collection: July 2024
                Volume: 14
                Issue: 7 ( doiID: 10.1002/ctm2.v14.7 )
                Electronic Location Identifier: e1769
                Affiliations
                [ 1 ] Department of Computational and Systems Biology, School of Medicine University of Pittsburgh Pittsburgh Pennsylvania USA
                Author notes
                [*] [* ] Correspondence

                Robin E. C. Lee, Department of Computational and Systems Biology, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.

                Email: RobinLee@ 123456pitt.edu

                Author information
                https://orcid.org/0000-0001-7209-3929
                Article
                Publisher ID: CTM21769
                DOI: 10.1002/ctm2.1769
                PMC ID: 11255019
                PubMed ID: 39021054
                SO-VID: e6becf1f-1724-4bd2-9257-d69c3cb508cb
                Copyright © © 2024 The Author(s). Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.
                License:

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 16 June 2024
                Date accepted : 08 July 2024
                Page count
                Figures: 1, Tables: 1, Pages: 7, Words: 4383
                Funding
                Funded by: National Institute of General Medical Sciences , doi 10.13039/100000057;
                Award ID: R35‐GM119462
                Categories
                Subject: Commentary
                Subject: Commentary
                Custom metadata
                source-schema-version-number 2.0
                cover-date July 2024
                details-of-publishers-convertor Converter:WILEY_ML3GV2_TO_JATSPMC version:6.4.5 mode:remove_FC converted:18.07.2024

                ScienceOpen disciplines: Medicine
                Keywords: deubiquitylating enzyme,precision medicine,ubiquitin,ubiquitin modifying enzymes
                Data availability:
                ScienceOpen disciplines: Medicine
                Keywords: deubiquitylating enzyme, precision medicine, ubiquitin, ubiquitin modifying enzymes

                Comments

                Comment on this article