Review
Cell Biology
Austin Folger, Yanchang Wang
Summary: Protein misfolding and aggregation play a crucial role in neurodegenerative diseases, including Huntington's, where polyglutamine expansions lead to protein aggregation. Cells employ the ubiquitin-proteasome system and autophagy pathways to degrade misfolded proteins, emphasizing the importance of efficient protein degradation for cell health.
Article
Plant Sciences
Yusaku Sadahiro, Yuki Hitora, Sachiko Tsukamoto
Summary: This study identified a compound from the extract of Colletotrichum sp. that can target mutant p53 in cancer cells, inhibiting the growth of cancer cells and decreasing mutant p53 levels.
JOURNAL OF NATURAL PRODUCTS
(2021)
Article
Biochemistry & Molecular Biology
Arnaud Marquette, Christopher Aisenbrey, Burkhard Bechinger
Summary: Membrane interactions accelerate the oligomerisation and beta-amyloid fibril formation of htt17-polyglutamine segments. The kinetics of fibre formation is strongly dependent on the presence of lipids, the length of the polyQ expansion, and the polypeptide-to-lipid ratio.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Medicine, Research & Experimental
Brigida R. Pinho, Liliana M. Almeida, Michael R. Duchen, Jorge M. A. Oliveira
Summary: The use of YM-1 can effectively modulate huntingtin protein proteostasis, reducing aggregation and enhancing degradation, making it a potential approach for treating Huntington's disease.
Article
Cell Biology
Gun West, Minttu Turunen, Anna Aalto, Laura Virtanen, Song-Ping Li, Tiina Helio, Annika Meinander, Pekka Taimen
Summary: This study reveals the intricate interplay between mutant lamins A and C and the protein degradation machinery. Mutant lamins A and C reduce the activity of the ubiquitin-proteasome system (UPS), leading to accumulation of K48-ubiquitin chains. However, compensatory enhanced autophagy can degrade the mutant lamins A and C. Furthermore, pharmacological interventions that enhance protein degradation can be beneficial for maintaining cellular homeostasis.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Dingding Zhou, Xiaohong Wang, Xiangfeng Wang, Tonglin Mao
Summary: PIF4 regulates microtubule organization through the PUB31-SPR1 module to promote hypocotyl cell elongation under high temperature.
Article
Chemistry, Multidisciplinary
Xiao-jing Li, Yuan-yuan Zhang, Yu-hua Fu, Hao Zhang, He-xuan Li, Quan-fu Li, Hai-ling Li, Ren-ke Tan, Chen-xiao Jiang, Wei Jiang, Zeng-xia Li, Cheng Luo, Bo-xun Lu, Yong-jun Dang
Summary: Huntington's disease is a neurodegenerative disorder caused by toxic aggregates of mutant huntingtin protein in the brain. Inhibiting the activity of Valosin-containing protein, a crucial regulator of proteostasis, could be a potential therapeutic strategy for HD. Gossypol, a drug approved in China, has been identified as a novel modulator of VCP that shows promise in treating HD by reducing levels of mutant huntingtin protein.
ACTA PHARMACOLOGICA SINICA
(2021)
Article
Oncology
Minhong Tang, John Crown, Michael J. Duffy
Summary: The mutant p53 reactivating drug, COTI-2, was found to degrade MYC and synergistically inhibit tumor cell growth when used in combination with the MYC inhibitor, MYCi975. This dual action of COTI-2 makes it a promising candidate for anticancer therapy.
INVESTIGATIONAL NEW DRUGS
(2023)
Review
Neurosciences
Mohamed A. Eldeeb, Mohamed A. Ragheb, Marwa H. Soliman, Richard P. Fahlman
Summary: Accumulation of protein aggregates and decreased cellular degradation capacity are prominent features in the development of aging-related neurodegenerative disorders. Repair or elimination of abnormal proteins is mediated by quality control mechanisms, such as chaperones. Autophagic-lysosomal system and ubiquitin-proteasome system are responsible for the selective degradation of abnormal protein fragments. The role of N-degrons in these processes is poorly understood.
NEUROTOXICITY RESEARCH
(2022)
Review
Biochemistry & Molecular Biology
Baohua Liu, Jing Ruan, Meng Chen, Zhongding Li, Gloria Manjengwa, Dirk Schlueter, Weihong Song, Xu Wang
Summary: Neurodegenerative diseases result from the aggregation of neurotoxic proteins in the central nervous system, often due to dysfunction in the ubiquitin-proteasome system and the autophagy-lysosomal pathway. Deubiquitinating enzymes (DUBs) play a key role in regulating protein degradation and have the potential to become therapeutic targets for neurodegenerative diseases by modulating the stability of pathogenic proteins and influencing processes like mitophagy and neuroinflammation.
MOLECULAR PSYCHIATRY
(2022)
Article
Endocrinology & Metabolism
Xin-Yi Liu, Xue-Jiao Chen, Miao Zhao, Zhi-qiang Wang, Hai-zhu Chen, Hong-Fu Li, Chen-Ji Wang, Shi-Fei Wu, Chao Peng, Yue Yin, Hong-Xia Fu, Min-Ting Lin, Long Yu, Zhi-Qi Xiong, Zhi-Ying Wu, Ning Wang
Summary: Late-onset MADD may be associated with mutations in the ETFDH gene, leading to instability and degradation of ETF:QO proteins. The study found that CHIP-dependent ubiquitin-proteasome pathway degradation may play a key role in the degradation of mutant ETF:QO proteins.
JOURNAL OF INHERITED METABOLIC DISEASE
(2021)
Article
Biotechnology & Applied Microbiology
Austine O. Ehibhatiomhan, Rahman Rahman Pour, Sebastien Farnaud, Timothy D. H. Bugg, Sharon Mendel-Williams
Summary: Expression of lignin-oxidising Pseudomonas fluorescens Dyp1B in the periplasm of Pseudomonas putida KT2440 enhances oxidation activity for DCP and polymeric lignin substrates. Mutagenesis studies reveal that specific amino acid mutations can increase oxidation activity for manganese ions and polymeric lignin. Expression of mutant genes as tat fusion proteins also enhances lignin oxidation by P. putida KT2440.
ENZYME AND MICROBIAL TECHNOLOGY
(2023)