Article
Biochemistry & Molecular Biology
Abramo J. Manfredonia, Daniel A. Kraut
Summary: The ubiquitin-proteasome system is responsible for protein degradation in eukaryotic cells. The study showed that degradation of ubiquitin-independent degrons (UbIDs) is slower and relies on loosely folded substrates. Furthermore, UbID degradation is ATP-independent.
Article
Cell Biology
Angeles C. Tecalco-Cruz, Jose Pedraza-Chaverri, Alfredo Briones-Herrera, Eduardo Cruz-Ramos, Lilia Lopez-Canovas, Jesus Zepeda-Cervantes
Summary: This review investigates the altered pathways involved in proteostasis in AD, suggesting that studying these pathways is critical for identifying new biomarkers and target molecules for AD.
MOLECULAR AND CELLULAR BIOCHEMISTRY
(2022)
Article
Cell Biology
Zhen Wei, Kuan Zeng, Jichang Hu, Xing Li, Fang Huang, Bin Zhang, Jian-Zhi Wang, Rong Liu, Hong-Lian Li, Xiaochuan Wang
Summary: This study reveals that the deubiquitinase USP10 is involved in Tau aggregation and is upregulated in Alzheimer's disease. Increased USP10 levels lead to elevated phosphorylation and binding of Tau protein, while decreasing its ubiquitination, promoting Tau aggregation and stabilization.
CELL DEATH & DISEASE
(2022)
Article
Multidisciplinary Sciences
Afu Fu, Victoria Cohen-Kaplan, Noa Avni, Ido Livneh, Aaron Ciechanover
Summary: The degradation of proteins through the ubiquitin-proteasome system is a complex multistep process that relies on the coordinated activity of various enzymes. Nuclear condensates containing essential components like p62 play a crucial role in protein quality control and degradation, especially under stress conditions. These assemblies, generated through liquid-liquid phase separation, efficiently facilitate proteolysis of nuclear proteins and unassembled proteasome subunits, indicating their involvement in cellular protein quality control.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Multidisciplinary Sciences
Holly A. Byers, Amy N. Brooks, Janakiram R. Vangala, Jacqueline M. Grible, Alex Feygin, Charles V. Clevenger, J. Chuck Harrell, Senthil K. Radhakrishnan
Summary: Proteasome subunit transcript levels are elevated in all breast cancer subtypes, with triple-negative breast cancer showing the highest sensitivity to proteasome inhibition. Targeting NRF1 could enhance the efficacy of proteasome inhibitors in triple-negative breast cancer.
SCIENTIFIC REPORTS
(2023)
Article
Biochemistry & Molecular Biology
Amit Kumar Singh Gautam, Houqing Yu, Christopher Yellman, Adrian H. Elcock, Andreas Matouschek
Summary: The proteasome is a powerful intracellular protease that can degrade any protein, self or foreign, through ubiquitin tagging. It consists of approximately 33 subunits, and their assembly and activity are regulated by post-translational modifications on long disordered regions of the subunits. Molecular modeling and biochemical experiments have shown that some disordered regions of proteasome subunits access the substrate recognition sites and are constructed from amino acid sequences that escape recognition.
Review
Biochemistry & Molecular Biology
Carolyn Allain Breckel, Mark Hochstrasser
Summary: The proper folding of proteins is vital for their diverse functions, and misfolded proteins can potentially harm cells by forming aggregates. Protein quality control pathways are responsible for repairing or degrading abnormal proteins, with the ubiquitin-proteasome system being commonly employed.
Article
Chemistry, Medicinal
Nobumichi Ohoka, Masanori Suzuki, Takuya Uchida, Genichiro Tsuji, Yoshinori Tsukumo, Masayuki Yoshida, Takao Inoue, Yosuke Demizu, Hitoshi Ohki, Mikihiko Naito
Summary: In this study, novel FLT3 degraders were developed by introducing an FDA-approved FLT3 inhibitor, gilteritinib, into targeted protein degradation technology. The most active compound, CRBN(FLT3)-8, potently degraded FLT3-ITD via the ubiquitin-proteasome system and effectively inhibited the proliferation of AML cells.
ACS MEDICINAL CHEMISTRY LETTERS
(2022)
Review
Biochemistry & Molecular Biology
Yanhui Zhou, Hakim Manghwar, Weiming Hu, Fen Liu
Summary: Autophagy is a key pathway for nutrient recycling in eukaryotes, influenced by various factors such as hormones, second messengers, post-transcriptional regulation, and protein post-translational modification. It is activated under stress conditions to help cells survive, and the degradation mechanism of autophagy-related proteins in different organisms has attracted attention.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Cell Biology
Yosup Kim, Eun-Kyung Kim, Yoona Chey, Min-Jeong Song, Ho Hee Jang
Summary: The proteasome is a multi-catalytic protease complex that regulates protein quality control. It selectively degrades cellular proteins through ubiquitination and plays a critical role in maintaining protein homeostasis. This article summarizes the proteasome's structure, regulatory mechanisms, proteins that control its activity, and its involvement in various diseases, chemoresistant cells, and cancer stem cells. Potential therapeutic modalities that target the ubiquitin-proteasome system are also discussed.
Article
Biochemistry & Molecular Biology
Apoorvi Tyagi, Saba Haq, Suresh Ramakrishna
Summary: Reactive oxygen species (ROS) play a dual role in cancer, with low levels being beneficial while excessive accumulation can lead to cancer progression. Recent studies have shown that deubiquitinating enzymes (DUBs) are regulated by ROS, with the oxidation of catalytic cysteine leading to reversible inactivation, offering potential new insights for anticancer therapeutics.
Review
Biochemistry & Molecular Biology
Xin Chen, Q. Ping Dou, Jinbao Liu, Daolin Tang
Summary: Understanding the mechanisms of protein homeostasis and the ubiquitin-proteasome system is crucial for investigating disease pathogenesis, with implications for potential therapeutic interventions. Impaired UPS pathways are implicated in various diseases, highlighting the importance of targeting this system for disease treatment.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Merav D. Shmueli, Daoud Sheban, Avital Eisenberg-Lerner, Yifat Merbl
Summary: Histones are key protein building blocks of chromatin, regulated by intricate mechanisms to control chromatin compaction and epigenetic regulation. Proteasome-dependent degradation, along with protein modifications, play roles in regulating histone stability, impacting cellular and physiological states.
Article
Multidisciplinary Sciences
Jennifer Cable, Eilika Weber-Ban, Tim Clausen, Kylie J. Walters, Michal Sharon, Daniel J. Finley, Yangnan Gu, John Hanna, Yue Feng, Sascha Martens, Anne Simonsen, Malene Hansen, Hong Zhang, Jonathan M. Goodwin, Alessio Reggio, Chunmei Chang, Liang Ge, Brenda A. Schulman, Raymond J. Deshaies, Ivan Dikic, J. Wade Harper, Ingrid E. Wertz, Nicolas H. Thoma, Mikolaj Slabicki, Judith Frydman, Ursula Jakob, Della C. David, Eric J. Bennett, Carolyn R. Bertozzi, Richa Sardana, Vinay V. Eapen, Serena Carra
Summary: Targeted protein degradation is essential for cellular function and development. This process involves tightly regulated protein degradation pathways to eliminate misfolded and aggregated proteins, adjust protein levels during cellular differentiation, and selectively eliminate target proteins. Understanding these pathways can provide insights into disease pathology and the development of novel therapeutics.
ANNALS OF THE NEW YORK ACADEMY OF SCIENCES
(2022)
Review
Pharmacology & Pharmacy
Si-Min Qi, Jinyun Dong, Zhi-Yuan Xu, Xiang-Dong Cheng, Wei-Dong Zhang, Jiang-Jiang Qin
Summary: PROTAC technology is an effective method for degrading target proteins through the ubiquitin-proteasome system, with promising applications in cancer treatment. The first oral PROTACs have shown encouraging results in clinical trials, sparking greater enthusiasm for PROTAC research.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Chemistry, Medicinal
Celeste Alverez, Stacie L. Bulfer, Ramappa Chakrasali, Michael S. Chimenti, Raymond J. Deshaies, Neal Green, Mark Kelly, Matthew G. LaPorte, Taber S. Lewis, Mary Liang, William J. Moore, R. Jeffrey Neitz, Vsevolod A. Peshkov, Michael A. Walters, Feng Zhang, Michelle R. Arkin, Peter Wipf, Donna M. Huryn
ACS MEDICINAL CHEMISTRY LETTERS
(2016)
Editorial Material
Biochemistry & Molecular Biology
Gary Kleiger, Raymond Deshaies
Letter
Biochemistry & Molecular Biology
Janakiram R. Vangala, Franziska Sotzny, Elke Krueger, Raymond J. Deshaies, Senthil K. Radhakrishnan
Article
Biochemistry & Molecular Biology
Veronika Reiterer, Cristina Figueras-Puig, Francois Le Guerroue, Stefano Confalonieri, Manuela Vecchi, Dasaradha Jalapothu, Sandip M. Kanse, Raymond J. Deshaies, Pier Paolo Di Fiore, Christian Behrends, Hesso Farhan
Article
Biochemical Research Methods
Liang Xue, Emily E. Blythe, Elyse C. Freiberger, Jennifer L. Mamrosh, Alexander S. Hebert, Justin M. Reitsma, Sonja Hess, Joshua J. Coon, Raymond J. Deshaies
MOLECULAR & CELLULAR PROTEOMICS
(2016)
Article
Cell Biology
Min-Kyung Sung, Justin M. Reitsma, Michael J. Sweredoski, Sonja Hess, Raymond J. Deshaies
MOLECULAR BIOLOGY OF THE CELL
(2016)
Article
Biochemistry & Molecular Biology
T. Van Nguyen, J. Eugene Lee, Michael J. Sweredoski, Seung-Joo Yang, Seung-Je Jeon, Joseph S. Harrison, Jung-Hyuk Yim, Sang Ghil Lee, Hiroshi Handa, Brian Kuhlman, Ji-Seon Jeong, Justin M. Reitsma, Chul-Seung Park, Sonja Hess, Raymond J. Deshaies
Article
Multidisciplinary Sciences
Soojay Banerjee, Alberto Bartesaghi, Alan Merk, Prashant Rao, Stacie L. Bulfer, Yongzhao Yan, Neal Green, Barbara Mroczkowski, R. Jeffrey Neitz, Peter Wipf, Veronica Falconieri, Raymond J. Deshaies, Jacqueline L. S. Milne, Donna Huryn, Michelle Arkin, Sriram Subramaniam
Article
Chemistry, Medicinal
Christian Perez, Jing Li, Francesco Parlati, Matthieu Rouffett, Yuyong Ma, Andrew L. Mackinnon, Tsui-Fen Chou, Raymond J. Deshaies, Seth M. Cohen
JOURNAL OF MEDICINAL CHEMISTRY
(2017)
Article
Biochemistry & Molecular Biology
Jing Li, Tanya Yakushi, Francesco Parlati, Andrew L. Mackinnon, Christian Perez, Yuyong Ma, Kyle P. Carter, Sharon Colayco, Gavin Magnuson, Brock Brown, Kevin Nguyen, Stefan Vasile, Eigo Suyama, Layton H. Smith, Eduard Sergienko, Anthony B. Pinkerton, Thomas D. Y. Chung, Amy E. Palmer, Ian Pass, Sonja Hess, Seth M. Cohen, Raymond J. Deshaies
NATURE CHEMICAL BIOLOGY
(2017)
Article
Biochemistry & Molecular Biology
Linda Lauinger, Jing Li, Anton Shostak, Ibrahim Avi Cemel, Nati Ha, Yaru Zhang, Philipp E. Merkl, Simon Obermeyer, Nicolas Stankovic-Valentin, Tobias Schafmeier, Walter J. Wever, Albert A. Bowers, Kyle P. Carter, Amy E. Palmer, Herbert Tschochner, Frauke Melchior, Raymond J. Deshaies, Michael Brunner, Axel Diernfellner
NATURE CHEMICAL BIOLOGY
(2017)
Article
Multidisciplinary Sciences
Thang Van Nguyen, Jing Li, Chin-Chun (Jean) Lu, Jennifer L. Mamrosh, Gang Lu, Brian E. Cathers, Raymond J. Deshaies
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2017)
Article
Biochemistry & Molecular Biology
Mark A. Nakasone, Timothy A. Lewis, Olivier Walker, Anita Thakur, Wissam Mansour, Carlos A. Castaneda, Jennifer L. Goeckeler-Fried, Frank Parlati, Tsui-Fen Chou, Ortal Hayat, Daoning Zhang, Christina M. Camara, Steven M. Bonn, Urszula K. Nowicka, Susan Krueger, Michael H. Glickman, Jeffrey L. Brodsky, Raymond J. Deshaies, David Fushman
Review
Multidisciplinary Sciences
Raymond J. Deshaies
Article
Biochemistry & Molecular Biology
Justin M. Reitsma, Xing Liu, Kurt M. Reichermeier, Annie Moradian, Michael J. Sweredoski, Sonja Hess, Raymond J. Deshaies