Article
Biochemistry & Molecular Biology
Yu-Shan Chen, Xia Han, Kui Lin, Tian-Xia Jiang, Xiao-Bo Qiu
Summary: The study revealed that Blm10 promotes degradation of core histones and regulates transcription in yeast, particularly in genes related to translation, amino acid metabolism, and carbohydrate metabolism, especially during cellular aging. Mutations in Blm10's putative acetyl-lysine binding region disrupt its regulation of gene expression.
Article
Biochemistry & Molecular Biology
Katarzyna Cekala, Karolina Trepczyk, Daria Sowik, Przemyslaw Karpowicz, Artur Gieldon, Julia Witkowska, Malgorzata Gizynska, Elzbieta Jankowska, Ewa Wieczerzak
Summary: In this study, we designed and obtained a series of peptidomimetic stimulators of 20S proteasome, which can enhance protein degradation and increase the activity of proteasome in cells. These compounds may have the potential to counteract proteasome impairment in patients with age-related diseases.
Article
Biochemistry & Molecular Biology
Alicia Burris, Kenrick A. Waite, Zachary Reuter, Samuel Ockerhausen, Jeroen Roelofs
Summary: The proteasome selectively degrades proteins and consists of different complexes, which are poorly understood in terms of regulation and response to changing physiological conditions. The study focused on Blm10 and RP, showing that controlling Blm10 levels affects the formation of RP-CP complexes through autophagy. Reducing Blm10 levels can increase CP-binding surfaces and impact proteasome function, providing important insights into maintaining the proteasome landscape.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Medicine, Research & Experimental
Tian-Xia Jiang, Shuang Ma, Xia Han, Zi-Yu Luo, Qian-Qian Zhu, Tomoki Chiba, Wei Xie, Kui Lin, Xiao-Bo Qiu
Summary: The research revealed that PA200 plays a crucial role in maintaining the stability of histone marks by promoting the degradation of core histones. Deficiency of PA200 leads to aging-related diseases, such as immune malfunction and shorter lifespan.
Article
Biology
Tatjana von Rosen, Monika Pepelnjak, Jan-Philipp Quast, Paola Picotti, Eilika Weber-Ban
Summary: Mycobacteria and other actinobacteria possess proteasomal degradation pathways. This study reveals the crucial role of proteasomal degradation in the survival of bacteria in adverse environments. The mechanism of substrate selection and processing by the Bpa-proteasome complex is investigated, and it is found that the disorder in substrates and the unstructured tail of the substrate play important roles. The heat shock chaperone DnaK stabilizes the substrate against Bpa-mediated proteasomal degradation. Phenotypical characterization supports the importance of Bpa-dependent proteasomal degradation in the survival of the bacterium under stress conditions.
LIFE SCIENCE ALLIANCE
(2023)
Review
Biochemistry & Molecular Biology
Ayse Seda Yazgili, Frederic Ebstein, Silke Meiners
Summary: This article discusses the role and dysregulation of the proteasome regulator PA200 in human diseases, highlighting its potential as a therapeutic target in cancer.
Article
Biochemistry & Molecular Biology
Ban Sato, Jiwoo Kim, Kazunori Morohoshi, Woojin Kang, Kenji Miyado, Fuminori Tsuruta, Natsuko Kawano, Tomoki Chiba
Summary: PA200 and ECPAS proteins work together during spermatogenesis and are crucial for male fertility.
Review
Medicine, Research & Experimental
Adria Hasan, Suroor Fatima Rizvi, Sana Parveen, Snober S. Mir
Summary: Cells may undergo DNA damage due to various stressors, leading to altered cell function and diseases such as cancer. DNA repair mechanisms play a crucial role in maintaining genome stability, with heat shock proteins (HSPs) being key players in this adaptive response. Modulating protein quality control systems like the HSPs network could be a promising strategy for targeting diseases associated with genomic instability, such as cancer.
Article
Biochemistry & Molecular Biology
Jeffrey C. Hsiao, Atara R. Neugroschl, Ashley J. Chui, Cornelius Y. Taabazuing, Andrew R. Griswold, Qinghui Wang, Hsin-Che Huang, Elizabeth L. Orth-He, Daniel P. Ball, Giorgos Hiotis, Daniel A. Bachovchin
Summary: CARD8, a pattern-recognition receptor, is involved in the activation of the inflammasome. The degradation of CARD8 by the 20S proteasome plays a crucial role in the control of inflammasome activation.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Helena M. Schnell, Jessie Ang, Shaun Rawson, Richard M. Walsh, Yagmur Micoogullari, John Hanna
Summary: The proteasome, a complex responsible for protein degradation, has gates in its central core particle (CP) that control substrate access. These gates are opened by the regulatory particle (RP). Recent research has shown that the CP assembly chaperones Pba1/2 can also mediate gate opening through a unique structural arrangement. In this study, a detailed analysis of CP gate modulation by Pba1/2 was conducted, revealing that Pba1/2 can regulate the gates through direct interactions and disrupt the closed state. This novel mechanism appears to be specific to Pba1/2 and occurs during proteasome assembly.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Dennis C. Koester, Vanessa M. Marx, Sarah Williams, Jan Jiricek, Maxime Dauphinais, Olivier Rene, Sarah L. Miller, Lei Zhang, Debjani Patra, Yen-Liang Chen, Harry Cheung, Jonathan Gable, Suresh B. Lakshminarayana, Colin Osborne, Jean-Rene Galarneau, Upendra Kulkarni, Wendy Richmond, Angela Bretz, Linda Xiao, Frantisek Supek, Christian Wiesmann, Srinivas Honnappa, Celine Be, Pascal Maeser, Marcel Kaiser, Ryan Ritchie, Michael P. Barrett, Thierry T. Diagana, Christopher Sarko, Srinivasa P. S. Rao
Summary: This study presents a brain-penetrant, parasite-selective 20S proteasome inhibitor for the treatment of Human African Trypanosomiasis. The study utilized cryo-electron microscopy and an in silico model to guide hit expansion and lead optimization. In vitro and in vivo experiments successfully identified compounds with potential to cure the disease.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Review
Biochemistry & Molecular Biology
Deepa Kumari, Jeffrey L. Brodsky
Summary: Protein quality control processes are crucial for cellular and organism health, particularly for polypeptides entering the endoplasmic reticulum (ER). ER-associated degradation (ERAD) is a multi-step pathway that targets inefficiently matured proteins for degradation, providing a mechanism to regulate protein levels and activities in the ER.
Article
Biochemistry & Molecular Biology
Richard M. Walsh Jr, Shaun Rawson, Helena M. Schnell, Benjamin Velez, Tamayanthi Rajakumar, John Hanna
Summary: The assembly of the proteasome's core particle involves the collaboration of chaperones and subunit propeptides. Through cryogenic electron microscopy, this study reveals the structure of a post-fusion assembly intermediate of the proteasome, clarifying the role of associated factors in CP assembly and maturation.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Anna Fidor, Katarzyna Cekala, Ewa Wieczerzak, Marta Ceglowska, Franciszek Kasprzykowski, Christine Edwards, Hanna Mazur-Marzec
Summary: Nostocyclopeptides, bioactive nonribosomal peptides produced by cyanobacteria of the genus Nostoc, have been shown to selectively inhibit specific activities of the 20S proteasome, suggesting their potential as regulators of cellular processes.
Article
Biochemistry & Molecular Biology
Richard M. Walsh, Shaun Rawson, Helena M. Schnell, Benjamin Velez, Tamayanthi Rajakumar, John Hanna
Summary: The assembly of the proteasome's core particle (CP) requires chaperones and subunit propeptides. The study reveals the structural changes induced by midline-spanning interactions and the role of chaperones in the maturation process. The results suggest that cleavage may not be sufficient for propeptide release and propose a scaffolding role for chaperones in CP fusion and activation.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2023)
Article
Cell Biology
Andrew S. Lyon, Genevieve Morin, Michelle Moritz, King Clyde B. Yabut, Tamira Vojnar, Alex Zelter, Eric Muller, Trisha N. Davis, David A. Agard
MOLECULAR BIOLOGY OF THE CELL
(2016)
Article
Cell Biology
Shruthi Viswanath, Massimiliano Bonomi, Seung Joong Kim, Vadim A. Klenchin, Keenan C. Taylor, King C. Yabut, Neil T. Umbreit, Heather A. Van Epps, Janet Meehl, Michele H. Jones, Daniel Russel, Javier A. Velazquez-Muriel, Mark Winey, Ivan Rayment, Trisha N. Davis, Andrej Sali, Eric G. Muller
MOLECULAR BIOLOGY OF THE CELL
(2017)
Article
Biotechnology & Applied Microbiology
Richard Ramsden, Luther Arms, Trisha N. Davis, Eric G. D. Muller
Article
Cell Biology
Michelle M. Shimogawa, Megan M. Wargacki, Eric G. Muller, Trisha N. Davis
Article
Cell Biology
Megan M. Wargacki, Jessica C. Tay, Eric G. Muller, Charles L. Asbury, Trisha N. Davis
Article
Biochemistry & Molecular Biology
Daniel A. Skelly, Gennifer E. Merrihew, Michael Riffle, Caitlin F. Connelly, Emily O. Kerr, Marnie Johansson, Daniel Jaschob, Beth Graczyk, Nicholas J. Shulman, Jon Wakefield, Sara J. Cooper, Stanley Fields, William S. Noble, Eric G. D. Muller, Trisha N. Davis, Maitreya J. Dunham, Michael J. MacCoss, Joshua M. Akey
Article
Biochemical Research Methods
Massimiliano Bonomi, Riccardo Pellarin, Seung Joong Kim, Daniel Russel, Bryan A. Sundin, Michael Riffle, Daniel Jaschob, Richard Ramsden, Trisha N. Davis, Eric G. D. Muller, Andrej Sali
MOLECULAR & CELLULAR PROTEOMICS
(2014)
Article
Cell Biology
Justin M. Kollman, Alex Zelter, Eric G. D. Muller, Bethany Fox, Luke M. Rice, Trisha N. Davis, David A. Agard
MOLECULAR BIOLOGY OF THE CELL
(2008)
Article
Cell Biology
Erin M. Mathieson, Yasuyuki Suda, Mark Nickas, Brian Snydsman, Trisha N. Davis, Eric G. D. Muller, Aaron M. Neiman
MOLECULAR BIOLOGY OF THE CELL
(2010)
Article
Cell Biology
Michele Haltiner Jones, Eileen T. O'Toole, Amy S. Fabritius, Eric G. Muller, Janet B. Meehl, Sue L. Jaspersen, Mark Winey
MOLECULAR BIOLOGY OF THE CELL
(2018)
Article
Biology
Axel F. Brilot, Andrew S. Lyon, Alex Zelter, Shruthi Viswanath, Alison Maxwell, Michael J. MacCoss, Eric G. Muller, Andrej Sali, Trisha N. Davis, David A. Agard
Summary: This study investigates the mechanisms of γ TuRC assembly using a combination of crosslinking mass spectrometry, X-ray crystallography, and cryo-EM structures. The results highlight the crucial role of the evolutionarily conserved CM1 motif in Spc110p in aiding γ TuRC assembly, showing that phosphorylation sites are mostly inhibitory. Comparison with the human γ TuRC structure reveals significant structural changes arising from CM1 helix binding in metazoan γ TuRC.
Article
Genetics & Heredity
Brianna R. King, Janet B. Meehl, Tamira Vojnar, Mark Winey, Eric G. Muller, Trisha N. Davis
Summary: The study utilized an inducible ectopic microtubule nucleation site in the nucleus of Saccharomyces cerevisiae to investigate the formation of a bipolar array and identified novel roles of microtubule-associated proteins and motors in microtubule nucleation.
Article
Biochemistry & Molecular Biology
John Mc Intyre, Eric G. D. Muller, Stefan Weitzer, Brian E. Snydsman, Trisha N. Davis, Frank Uhlmann
Article
Cell Biology
Joshua A. Rosenberg, Gregory C. Tomlin, W. Hayes McDonald, Brian E. Snydsman, Eric G. Mullert, John R. Yates, Kathleen L. Gould
MOLECULAR BIOLOGY OF THE CELL
(2006)