Article
Multidisciplinary Sciences
Man Pan, Qingyun Zheng, Tian Wang, Lujun Liang, Junxiong Mao, Chong Zuo, Ruichao Ding, Huasong Ai, Yuan Xie, Dong Si, Yuanyuan Yu, Lei Liu, Minglei Zhao
Summary: This study reveals the mechanism of the N-degron pathway mediated by Ubr1, including key structural elements involved in the initiation and elongation steps of ubiquitination.
Article
Plant Sciences
Aida Kozlic, Nikola Winter, Theresia Telser, Jakob Reimann, Katrin Rose, Lilian Nehlin, Sophie Berckhan, Gunjan Sharma, Charlene Dambire, Tinne Boeckx, Michael J. Holdsworth, Andreas Bachmair
Summary: The N-degron pathway is a branch of the ubiquitin-proteasome system that uses amino-terminal residues as degradation signals. This study reconstituted part of the plant N-degron pathway by expressing two enzymes from Arabidopsis thaliana in a mutated Saccharomyces cerevisiae strain. A novel assay was developed to monitor the stability of GFP-linked plant proteins with Arginine N-degrons.
FRONTIERS IN PLANT SCIENCE
(2022)
Article
Multidisciplinary Sciences
Amy M. Weeks, James R. Byrnes, Irene Lui, James A. Wells
Summary: This study utilized a new technology targeting the cell membrane (subtiligase-TM) to efficiently capture cell surface N termini, successfully sequencing 807 N termini and quantifying their changes in response to stimuli inducing proteolytic remodeling of the cell surface proteome. The development of the ASCENT database facilitates exploration of extracellular N termini, promoting a deeper understanding of extracellular protease biology.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Oncology
Angelo Cirinelli, Justin Wheelan, Christopher Grieg, Carlos A. Molina
Summary: This study identified 28 proteins that interact with ICER and focused on the roles of NAA15 and UBR4 in ICER proteasomal degradation. The results showed that the N-terminus of ICER is important for its interaction with UBR4 and its regulation by ubiquitination. Furthermore, it was found that (N)HAICER is more efficient in inhibiting transcription and inducing apoptosis compared to ICER(C)HA.
EXPERIMENTAL CELL RESEARCH
(2022)
Article
Multidisciplinary Sciences
Ulises H. H. Guzman, Henriette Aksnes, Rasmus Ree, Nicolai Krogh, Magnus E. E. Jakobsson, Lars J. J. Jensen, Thomas Arnesen, Jesper V. V. Olsen
Summary: Protein N-terminal (Nt) acetylation is a common modification in eukaryotes and plays a crucial role in promoting stability of the proteome. However, the functional impact of Nt-acetylation has been hindered by its pleiotropic effects. In this study, we used proteomics approaches to analyze the effects of NatA deficiency in Saccharomyces cerevisiae and found that it leads to global proteome remodeling and decreased thermostability of ribosomes.
NATURE COMMUNICATIONS
(2023)
Review
Oncology
Mohamed A. Eldeeb
Summary: In mammalian cells, intracellular protein degradation is mediated selectively by the Ubiquitin-Proteasome System (UPS) and autophagic-lysosomal system. Recent advances have shown the potential therapeutic implications of targeting N-degron proteolytic pathways to sensitize cancer cells to chemotherapeutic agents and inhibit growth of breast cancer cells. UPS-mediated protein degradation plays a crucial role in regulating cellular processes such as cell division, differentiation, and demise.
ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY
(2021)
Article
Multidisciplinary Sciences
Giuseppe Balistreri, Yohei Yamauchi, Tambet Teesalu
Summary: Many animal viruses, including the new coronavirus, have surface proteins that interact with host furin and furin-like proteases, which then bind to NRPs receptors on the cell surface. This interaction could play a significant role in virus transmission and pathogenesis.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biochemistry & Molecular Biology
Indrajit Sahu, Monika Bajorek, Xiaolin Tan, Madabhushi Srividya, Daria Krutauz, Noa Reis, Pawel A. Osmulski, Maria E. Gaczynska, Michael H. Glickman
Summary: The active sites of the 26S proteasome are located in the catalytic chamber of its 20S core particle. Access to this chamber is through a narrow channel formed by the seven outer alpha subunits. The gate blocking this channel is formed by the N-termini of neighboring alpha subunits, and attachment of activators rearranges these N-termini, allowing entry of substrates. A hydrogen bond between an invariant tyrosine (Y) in each subunit and a conserved aspartate (D) in its counterclockwise neighbor stabilizes the open state, except for the alpha 1-alpha 2 pair which leaves a gap in the ring. The third residue (X) of the YD(X) motif aligns with the open channel, and deletion of the alpha 2 N-terminal tail attenuates proteolysis despite the appearance of an open gate state.
Article
Genetics & Heredity
Leslie M. Stevens, Goheun Kim, Theodora Koromila, John W. Steele, James McGehee, Angelike Stathopoulos, David S. Stein
Summary: The development of a new photo-N-degron allows for light-dependent degradation of proteins in vivo, providing a potential tool for optogenetic studies. Comparisons with other light-dependent degrons show that the photo-N-degron and the B-LID domain are effective in inducing light-dependent protein degradation, while the photosensitive degron is less effective. Careful selection of inducible degrons is crucial for studying protein function in vivo.
Article
Microbiology
Rajani Ravishankar, Emily R. Hildebrandt, Grace Greenway, Nadeem Asad, Sangram Gore, Timothy M. Dore, Walter K. Schmidt
Summary: CAAX proteins undergo various posttranslational modifications, and this study used a proteolysis-resistant CAAX sequence to investigate Saccharomyces cerevisiae Ras2 GTPase. The results showed that the type of CAAX motif affected Ras2 protein levels, localization, and function.
MICROBIOLOGY SPECTRUM
(2023)
Article
Multidisciplinary Sciences
Thomas Ede, Raphaela E. Woodroffe, Marina A. G. von Keyserlingk, Daniel M. Weary
Summary: The study aimed to investigate whether calves followed the 'peak-end' rule in their memory of a painful procedure (disbudding). Conditioned place aversion and reflex pain behaviors were used as proxies for retrospective and 'real-time' reports of pain. The results did not support the existence of a peak-end effect in calves' memory of pain.
SCIENTIFIC REPORTS
(2023)
Article
Gastroenterology & Hepatology
Gennaro D'Amico, Luigi Maruzzelli, Aldo Airoldi, Ioannis Petridis, Giulia Tosetti, Antonio Rampoldi, Mario D'Amico, Roberto Miraglia, Stella De Nicola, Vincenzo La Mura, Marco Solcia, Riccardo Volpes, Giovanni Perricone, Cristiano Sgrazzutti, Angelo Vanzulli, Massimo Primignani, Angelo Luca, Giuseppe Malizia, Alessandro Federico, Marcello Dallio, Angelo Andriulli, Angelo Iacobellis, Luigi Addario, Matteo Garcovich, Antonio Gasbarrini, Luchino Chessa, Francesco Salerno, Giulia Gobbo, Manuela Merli, Lorenzo Ridola, Gianluca Svegliati Baroni, Giuseppe Tarantino, Nicola Caporaso, Filomena Morisco, Pietro Pozzoni, Agostino Colli, Luca Saverio Belli
Summary: While the discriminative ability of the MELD score is generally considered acceptable, its calibration is still unclear, especially in non-viral cirrhosis. The study suggests recalibrating the MELD and updating it with candidate variables.
JOURNAL OF HEPATOLOGY
(2021)
Article
Biology
Ilia Kats, Christian Reinbold, Marc Kschonsak, Anton Khmelinskii, Laura Armbruster, Thomas Ruppert, Michael Knop
Summary: N-terminal acetylation is an important protein modification and inactivation of N-terminal acetyltransferases (NATs) leads to protein homeostasis stress. This study found that NatA mutants exhibited increased activity of the ubiquitin proteasome system, while NatB or NatC mutants did not. The study revealed several mechanisms contributing to this behavior, including the regulation of protein abundance by NatA-mediated acetylation, increased abundance of E3 ligases in cells lacking NatA, and the identification of a novel chain-elongating enzyme Tom1 involved in the degradation of linear ubiquitin fusions.
LIFE SCIENCE ALLIANCE
(2022)
Review
Microbiology
Antonia Maria Romero, Maria Teresa Martinez-Pastor, Sergi Puig
Summary: Iron is essential for eukaryotic translation, affecting translation initiation, specific transcript translation repression, and various details of the translation process through the action of specific regulators. The influence of iron on different stages of translation and its correlation with protein biosynthesis control are key areas of research interest.
Review
Plant Sciences
Thierry Meinnel, Carmela Giglione
Summary: This review discusses the N-terminal modifications and their associated processing machinery in organisms with plastids gained through primary or secondary endosymbiosis. The N-terminus is a frequently modified site of proteins. Drawing primarily from knowledge gained from land plants, this review provides an overview of the modifications that alter protein N-terminal residues and presents updated information about the associated machinery, including the machinery in Archaeplastida. These modifications include various proteolytic events as well as additions of small groups such as acylation, arginylation, and oxidation. The landscape of N-terminal modifications dedicated to plastids is more complex compared to that of mitochondria. In addition, this review extends to plastid-containing Chromalveolata, including Stramenopiles, Apicomplexa, and Rhizaria. A well-conserved machinery, especially in the plastid, is reported. Examination of the two most abundant proteins on Earth, Rubisco and actin, reveals the complexity of N-terminal modification processes. The transfer of genes from the plastid to the nuclear genome during evolution is exemplified by the N-terminus modification machinery, which appears to be one of the latest transferred to the nuclear genome along with crucial major photosynthetic landmarks. This is supported by the greater number of plastid genes in Paulinellidae and red algae, which are the most recent and fossil recipients of primary endosymbiosis.
JOURNAL OF EXPERIMENTAL BOTANY
(2022)
Article
Biochemistry & Molecular Biology
Jin Seok Kim, Charlotte Saint-Andre, Hye Seong Lim, Cheol-Sang Hwang, Jean Marc Egly, Yunje Cho
JOURNAL OF BIOLOGICAL CHEMISTRY
(2015)
Article
Multidisciplinary Sciences
Hwa-Young Sun, Nari Kim, Cheol-Sang Hwang, Joo-Yeon Yoo
Article
Biochemistry & Molecular Biology
Brandon Wadas, Jimo Borjigin, Zheping Huang, Jang-Hyun Oh, Cheol-Sang Hwang, Alexander Varshavsky
JOURNAL OF BIOLOGICAL CHEMISTRY
(2016)
Article
Biochemistry & Molecular Biology
Mi-Jeong Park, Ren Sheng, Antonina Silkov, Da-Jung Jung, Zhi-Gang Wang, Yao Xin, Hyunjin Kim, Pallavi Thiagarajan-Rosenkranz, Seohyeon Song, Youngdae Yoon, Wonhee Nam, Ilshin Kim, Eui Kim, Dong-Gyu Lee, Yong Chen, Indira Singaram, Li Wang, Myoung Ho Jang, Cheol-Sang Hwang, Barry Honig, Sungho Ryu, Justin Lorieau, You-Me Kim, Wonhwa Cho
Review
Biochemistry & Molecular Biology
Kang-Eun Lee, Ji-Eun Heo, Jeong-Mok Kim, Cheol-Sang Hwang
MOLECULES AND CELLS
(2016)
Article
Biochemistry & Molecular Biology
Kha The Nguyen, Chang-Seok Lee, Sang-Hyeon Mun, Nhung Thimy Truong, Sang Ki Park, Cheol-Sang Hwang
JOURNAL OF BIOLOGICAL CHEMISTRY
(2019)
Article
Multidisciplinary Sciences
Jeong-Mok Kim, Ok-Hee Seok, Shinyeong Ju, Ji-Eun Heo, Jeonghun Yeom, Da-Som Kim, Joo-Yeon Yoo, Alexander Varshavsky, Cheolju Lee, Cheol-Sang Hwang
Article
Biochemistry & Molecular Biology
Kha The Nguyen, Jeong-Mok Kim, Sang-Eun Park, Cheol-Sang Hwang
JOURNAL OF BIOLOGICAL CHEMISTRY
(2019)
Article
Cell Biology
Kha The Nguyen, Sang-Hyeon Mun, Jihye Yang, Jongeun Lee, Ok-Hee Seok, Eunjeong Kim, Dasom Kim, So Young An, Dong-Young Seo, Jeong-Yong Suh, Yoontae Lee, Cheol-Sang Hwang
Summary: This study identifies MARCHF6 as a previously unknown NADPH sensor in the ubiquitin system and a crucial regulator of ferroptosis. MARCHF6 acts as an NADPH sensor to suppress ferroptosis by enhancing the degradation of pro-ferroptosis proteins.
NATURE CELL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Dong-Young Seo, Dasom Kim, Kha The Nguyen, Junsoo Oh, Jung -Shin Lee, Cheol-Sang Hwang
Summary: Our recent research demonstrates the production of Nt-arginylated ubiquitin in yeast, but its existence in multicellular organisms is unknown. In this study, we investigated the mechanism of Nt-arginylation of ubiquitin using HEK293 cells expressing various Nt-modified ubiquitins. We found that Nt-deamidase NTAQ1 converts Gln-starting ubiquitin into Glu-starting ubiquitin, which is then Nt-arginylated by arginyltransferase ATE1 in HEK293 cells. Moreover, the resulting RE-Ub is attached to the Lys119 residue of histone H2A by RING1B E3 ubiquitin ligase. These findings reveal a previously unknown type of histone ubiquitylation, significantly increasing the complexity of histone and ubiquitin codes.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)
Review
Cell Biology
Jihye Yang, Yoontae Lee, Cheol-Sang Hwang
Summary: This article summarizes the roles of NADPH metabolism and the ubiquitin-proteasome system in regulating ferroptosis, and highlights the emerging importance of MARCHF6 as a vital connector between NADPH metabolism and ferroptosis.
TRENDS IN CELL BIOLOGY
(2023)
Article
Cell Biology
Sang-Hyeon Mun, Chang-Seok Lee, Hyun Jin Kim, Jiye Kim, Haena Lee, Jihye Yang, Sin-Hyeo Im, Joung-Hun Kim, Je Kyung Seong, Cheol-Sang Hwang
Summary: The cytosol-retained POMC induces ER stress and ferroptotic cell death. It accelerates degradation of the glutathione peroxidase Gpx4, a core regulator of ferroptosis, via chaperone-mediated autophagy. The Marchf6 E3 ubiquitin ligase mediates the degradation of cytosol-retained POMC, preventing ER stress and ferroptosis. POMC-Cre-mediated Marchf6-deficient mice exhibit hyperphagia, reduced energy expenditure, and weight gain.
Article
Biochemistry & Molecular Biology
Kha The Nguyen, Shinyeong Ju, Sang-Yoon Kim, Chang-Seok Lee, Cheolju Lee, Cheol-Sang Hwang
Summary: Ubiquitin can undergo N-terminal modifications, including N-terminal methionine excision, N-terminal deamination, and N-terminal arginylation. N-terminal arginylation of ubiquitin and its conjugated proteins are upregulated during the stationary-growth phase or under oxidative stress. This discovery expands the complexity of the ubiquitin code.
MOLECULES AND CELLS
(2022)
Review
Biochemistry & Molecular Biology
Kha The Nguyen, Sang-Hyeon Mun, Chang-Seok Lee, Cheol-Sang Hwang
EXPERIMENTAL AND MOLECULAR MEDICINE
(2018)
Article
Cell Biology
Konstantin I. Piatkov, Tri T. M. Vu, Cheol-Sang Hwang, Alexander Varshavsky