Article
Hematology
Guus J. J. E. Heynen, Francis Baumgartner, Michael Heider, Upayan Patra, Maximilian Holz, Jan Braune, Melanie Kaiser, Isabell Schaeffer, Stefanos A. Bamopoulos, Evelyn Ramberger, Arunima Murgai, Yuen Lam Dora Ng, Uta Margareta Demel, Dominik Laue, Sven Liebig, Josefine Krueger, Martin Janz, Axel Nogai, Markus Schick, Philipp Mertins, Stefan Mueller, Florian Bassermann, Jan Kroenke, Ulrich Keller, Matthias Wirth
Summary: Proteasome inhibition is a highly effective treatment for multiple myeloma, but patients often develop resistance to proteasome inhibitors. Increased SUMOylation has been found in relapsed/refractory MM, and high expression of the SUMO E1-activating enzyme is associated with poor survival. Combination therapy with the SUMO E1-activating enzyme inhibitor and proteasome inhibitor showed synergy in MM cell lines and primary MM cells. Activated SUMOylation can be a therapeutic target for MM and combined SUMO/proteasome inhibition may be a potential strategy for treating proteasome inhibitor-resistant MM.
Review
Cell Biology
Marta Gomarasca, Giovanni Lombardi, Paola Maroni
Summary: Post-translational modifications, such as SUMOylation and NEDDylation, have significant roles in tumor cell biology, influencing various aspects of neoplastic transformation and evolution. This article focuses on the involvement and regulation of SUMOylation and NEDDylation in primary and secondary bone tumors, highlighting their potential in diagnostics and therapeutic strategies.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Krishna M. Chauhan, Yingxiao Chen, Yiyi Chen, Andrew T. Liu, Xiao-Xin Sun, Mu-Shui Dai
Summary: The study reveals that SENP1 is a critical p53 deSUMOylating enzyme, and its depletion induces p53 transactivation activity and synergizes with DNA damage-inducing agent etoposide to activate p53 and inhibit cancer cell growth.
JOURNAL OF CELLULAR BIOCHEMISTRY
(2021)
Review
Virology
Laurie-Anne Lamotte, Lionel Tafforeau
Summary: The review discusses how the NS1 protein of influenza A virus inhibits the host's antiviral response by disturbing ubiquitination.
Article
Biochemistry & Molecular Biology
Daniel Salas-Lloret, Roman Gonzalez-Prieto
Summary: Ubiquitination and SUMOylation are dynamic post-translational modifications that regulate cellular processes. The understanding of these modifications has been increased by the development of mass spectrometry-based approaches. This translated article provides a concise overview of the basic mechanisms of ubiquitination and SUMOylation, as well as recent MS-based approaches for specific target identification.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Genetics & Heredity
Irena J. J. Muffels, Imre F. Schene, Holger Rehmann, Maarten P. G. Massink, Maria M. van der Wal, Corinna Bauder, Martha Labeur, Natalia G. Armando, Maarten H. Lequin, Michiel L. Houben, Jaques C. Giltay, Saskia Haitjema, Albert Huisman, Fleur Vansenne, Judith Bluvstein, John Pappas, Lala V. Shailee, Yuri A. Zarate, Michal Mokry, Gijs W. van Haaften, Edward E. S. Nieuwenhuis, Damian Refojo, Femke van Wijk, Sabine A. Fuchs, Peter M. van Hasselt
Summary: Variants in NAE1 gene have been found to affect cellular pathways and disease pathophysiology. Decreased NAE1 abundance and overlapping clinical and cellular phenotypes support the pathogenicity of these variants. NAE1 is shown to play a role in protecting against cell death during cellular stress.
AMERICAN JOURNAL OF HUMAN GENETICS
(2023)
Article
Multidisciplinary Sciences
Hyein G. Lee, Abigail A. Lemmon, Christopher D. Lima
Summary: The Ufd1/Npl4/Cdc48 complex enhances unfolding of substrates modified by SUMO-polyubiquitin hybrid chains through interactions with SUMO. It exhibits a stronger effect on substrates modified by these chains compared to polyubiquitin chains when given a choice. Cryo-EM structures reveal the interactions between Ufd1/Npl4/Cdc48 and ubiquitin during the unfolding process. These findings confirm the significance of SUMO and ubiquitin modifications in cellular functions and support a model where Ufd1/Npl4/Cdc48, SUMO, and ubiquitin conjugation pathways converge to promote clearance of proteins modified with SUMO and polyubiquitin.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Editorial Material
Biochemistry & Molecular Biology
Xiaodong Cheng
Summary: Protein SUMOylation is an essential post-translational modification for maintaining cellular homeostasis. Recent evidence suggests that liquid-liquid phase separation (LLPS)/ biomolecular condensates play a role in regulating cellular SUMOylation, providing insights into its cellular mechanism.
TRENDS IN BIOCHEMICAL SCIENCES
(2023)
Article
Cell Biology
Arthur Aubry, Joel D. Pearson, Jason Charish, Tao Yu, Jeremy M. Sivak, Dimitris P. Xirodimas, Herve Avet-Loiseau, Jill Corre, Philippe P. Monnier, Rod Bremner
Summary: The neddylation inhibitor MLN4924/Pevonedistat is under clinical trials for various types of cancers. It shows efficacy by inhibiting multiple cellular networks and synergizing with standard-of-care drugs, potentially providing a broad therapeutic relevance.
Article
Cell Biology
Immacolata Giordano, Lucia Pirone, Veronica Muratore, Eukene Landaluze, Coralia Perez, Valerie Lang, Elisa Garde-Lapido, Monika Gonzalez-Lopez, Orhi Barroso-Gomila, Alfred C. O. Vertegaal, Ana M. Aransay, Jose Antonio Rodriguez, Manuel S. Rodriguez, James D. Sutherland, Rosa Barrio
Summary: The study investigates the interaction between two key transcription factors, CBX4 and SALL1, and reveals that increased SALL1 expression reduces the ubiquitination of CBX4, enhancing its stability. This leads to an increase in the number and size of CBX4-containing Polycomb bodies, resulting in greater repression of CBX4 target genes.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Wenjuan Zhang, Lihui Li, Lili Cai, Yupei Liang, Junfeng Xu, Yue Liu, Lisha Zhou, Chen Ding, Yanmei Zhang, Hu Zhao, Jun Qin, Zhimin Shao, Wenyi Wei, Lijun Jia
Summary: In this study, it was discovered that Prame recognizes p14/ARF for degradation. Inhibiting Prame expression and halting p14/ARF degradation can restrain tumor growth and induce G2/M phase cell cycle arrest.
CELL DEATH AND DIFFERENTIATION
(2021)
Article
Biochemistry & Molecular Biology
Audrey Dangoumau, Sylviane Marouillat, Roxane Coelho, Francois Wurmser, Celine Brulard, Shanez Haouari, Frederic Laumonnier, Philippe Corcia, Christian R. Andres, Helene Blasco, Patrick Vourc'h
Summary: Protein aggregates in motor neurons affected by ALS are associated with oxidative stress, which alters the expression of genes involved in ubiquitin and SUMO pathways. The combined effects of oxidative stress and ALS-related genetic mutations on gene expression highlight potential mechanisms underlying ALS pathophysiology and suggest targets for protecting motor neurons from neurodegeneration.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Cell Biology
Kartikeya Vijayasimha, Brian P. Dolan
Summary: NEDD8 is a ubiquitin-like protein that activates Cullin-Ring finger Ligases. Recent studies have identified non-canonical protein substrates of NEDD8, and the covalent modification of NEDD8 can alter the protein substrate.
Article
Multidisciplinary Sciences
Jie Li, Gregory J. Krause, Qi Gui, Susmita Kaushik, Gergely Rona, Qingyue Zhang, Feng-Xia Liang, Avantika Dhabaria, Carlos Anerillas, Jennifer L. Martindale, Nikita Vasilyev, Manor Askenazi, Beatrix Ueberheide, Evgeny Nudler, Myriam Gorospe, Ana Maria Cuervo, Michele Pagano
Summary: This study identifies a new function for mammalian SKP1 in the endolysosomes, which is independent of its established role as a component of ubiquitin ligases. SKP1 is found to be phosphorylated under nutrient-poor conditions, promoting V-ATPase assembly and acidification of late endosomes for degradation. Under nutrient-rich conditions, phosphorylated SKP1 is SUMOylated and allows unconventional secretion through interaction with SEC22B.
Article
Multidisciplinary Sciences
George Yakoub, Yun-Seok Choi, Ronald P. Wong, Tina Strauch, Kezia J. Ann, Robert E. Cohen, Helle D. Ulrich
Summary: This study describes the design and application of avidity-based probes against the ubiquitylated forms of PCNA in budding yeast. These probes can be tuned to regulate PCNA ubiquitylation and can be used as biosensors or inhibitors. In live cells, they reveal the timing and site-specific sensitivity of PCNA ubiquitylation.