Article
Biotechnology & Applied Microbiology
Qintao Wang, Yanbin Feng, Yandu Lu, Yi Xin, Chen Shen, Li Wei, Yuxue Liu, Nana Lv, Xuefeng Du, Wenqiang Zhu, Byeong-ryool Jeong, Song Xue, Jian Xu
Summary: This study identified methods to customize the chain length of fatty acids in Nannochloropsis, enabling the production of designer lipids with tailored properties. A mechanistic model was proposed to manipulate carbon distribution among fatty acids, laying the foundation for scalable production of designer lipids via industrial oleaginous microalgae.
METABOLIC ENGINEERING
(2021)
Article
Biochemistry & Molecular Biology
Hui Liu, Jingjing Cheng, Yongbing Zhou, Fangfang Liu, Nathan Griffin, Sam Faulkner, Li Wang
Summary: This study investigated the interaction between PFOA and Acot1 proteins, revealing that PFOA binds to Acot1 through electrostatic attraction and low strength non-covalent hydrogen bonding at a 1:1 molar ratio. Key amino acid residues N326 and H373 were identified as crucial regulators of this binding process. These findings provide insights into the specific molecular mechanisms that induce PFOA toxicity in humans and animals.
COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-TOXICOLOGY & PHARMACOLOGY
(2021)
Review
Cell Biology
Muhammad U. Anwar, F. Gisou van der Goot
Summary: S-acylation is an important posttranslational modification that regulates cellular processes. This reversible lipid modification affects cellular pathways and physiological processes, and the enzymes and proteins involved in S-acylation are still being discovered and studied.
JOURNAL OF CELL BIOLOGY
(2023)
Article
Microbiology
Robert W. B. Brown, Aabha Sharma, Miguel Rey Villanueva, Xiaomo Li, Ouma Onguka, Leeor Zilbermintz, Helen Nguyen, Ben A. Falk, Cheryl L. Olson, Joann M. Taylor, Conrad L. Epting, Rahul S. Kathayat, Neri Amara, Bryan C. Dickinson, Matthew Bogyo, David M. Engman
Summary: Dynamic post-translational modifications in eukaryotic cells allow rapid and specific regulation of protein functions. The S-acylation process involves reversible lipid modification of proteins, while depalmitoylation is necessary for acylation homeostasis. The identification of a homologue of human APT1 in Trypanosoma brucei, named TbAPT-L, suggests a lipase function rather than depalmitoylase activity, with modulation of TbAPT-L showing no effect on parasite growth or cellular depalmitoylation activity in vitro.
Article
Cell & Tissue Engineering
Changjiao Ji, Qiaoyan Dong, Huihui Liu, Xiaodeng Yang, Yingguang Han, Bingrui Zhu, Huaixin Xing
Summary: This study explored the mechanism of Acyl-protein thiesterase 1 (APT1) in senile osteoporosis (SOP). The results showed that APT1 was under-expressed in osteoblasts of bone tissue in SOP mice and its overexpression promoted osteoblast differentiation and bone formation. Mechanistically, APT1 activated the BMP/Smad pathway by regulating BMPR1a depalmitoylation, thus alleviating SOP.
REGENERATIVE THERAPY
(2023)
Article
Biochemistry & Molecular Biology
Qingwei Tian, Jingting Wu, Haifeng Xu, Zhangli Hu, Yangao Huo, Liyan Wang
Summary: This study reports the structure of the Photobacterium phosphoreum fatty acid reductase complex LuxC-LuxE and reveals the crucial conformational change in its catalytic mechanism. It also demonstrates that the activity of LuxC significantly affects bacterial luminescence reaction, and a mutant with improved activity has been identified. Furthermore, the study finds that luminous intensity mainly depends on the level of metabolic energy.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Qingjiang Hu, Takaaki Masuda, Kensuke Koike, Kuniaki Sato, Taro Tobo, Shotaro Kuramitsu, Akihiro Kitagawa, Atsushi Fujii, Miwa Noda, Yusuke Tsuruda, Hajime Otsu, Yosuke Kuroda, Shuhei Ito, Eiji Oki, Koshi Mimori
Summary: OSBPL3 is identified as a potential driver gene in gastric cancer, its overexpression activates the R-Ras/Akt signaling pathway and is associated with poor prognosis.
SCIENTIFIC REPORTS
(2021)
Article
Neurosciences
Fanny L. Lemarie, Nicholas S. Caron, Shaun S. Sanders, Mandi E. Schmidt, Yen T. N. Nguyen, Seunghyun Ko, Xiaohong Xu, Mahmoud A. Pouladi, Dale D. O. Martin, Michael R. Hayden
Summary: Research has shown that palmitoylation of mHTT and HIP14/HIP14L substrates is decreased early in Huntington's disease models, further decreasing with aging. Palmitoylation of mHTT can be normalized using an APT inhibitor, reducing mHTT aggregation and cytotoxicity.
NEUROBIOLOGY OF DISEASE
(2021)
Review
Cell Biology
Dillon S. Richardson, Jonathan M. Spehar, David T. Han, Prathik A. Chakravarthy, Steven T. Sizemore
Summary: RALA and RALB, highly homologous small G proteins belonging to the RAS superfamily, play important roles in regulating cellular functions and cancer development. Despite their similarities, they often display functional disparities in cancer, which remains an unanswered question.
Review
Multidisciplinary Sciences
Ruth Nussinov, Chung-Jung Tsai, Hyunbum Jang
Summary: Immunity plays a crucial role in both neurodevelopmental disorders and cancer, as the immune and nervous systems coevolve during embryonic development. Dysregulated signaling caused by germline or embryonic mutations can lead to changes in chromatin organization and gene accessibility, affecting the expression of essential genes in neurodevelopment. Similarly, dysregulated signaling resulting from somatic mutations contributes to cancer development. Both conditions involve small GTPases and their pathways, as well as dysregulation of TLRs, IL-1, GIT1, and FGFR signaling pathways. However, key differentiating factors are the timing and level of perturbation in specific cell types, indicating chromatin reorganization.
Article
Chemistry, Medicinal
Chuan Zhou, Zisheng Fan, Zehui Zhou, Yupeng Li, Rongrong Cui, Chaoyi Liu, Guizhen Zhou, Xingxing Diao, Hualiang Jiang, Mingyue Zheng, Sulin Zhang, Tianfeng Xu
Summary: Regulating SOS1 functions may lead to targeted therapy for pan-KRAS. Small-molecule SOS1 inhibitors have shown promise as anticancer agents, and the most advanced one, BI 1701963, is currently in phase I clinical studies. SOS1 agonists offer new opportunities for cancer treatment, but the underlying mechanisms still need further investigation. This study reports the discovery of the first SOS1 PROTACs, designed by connecting a VHL ligand to a known SOS1 agonist, ensuring that the observed inhibitory activity is due to degraders. The best compound, 9d, induced SOS1 degradation in various KRAS-driven cancer cells and exhibited superior antiproliferation activity compared to the agonist itself. Tumor xenograft study demonstrated the promising antitumor potency of 9d against human lung cancer. The study provides strong evidence for using agonists to design SOS1 PROTACs and demonstrates that targeted SOS1 degradation is an effective therapeutic strategy for overcoming KRAS-driven cancers.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Review
Pharmacology & Pharmacy
Yuran Qiu, Yuanhao Wang, Zongtao Chai, Duan Ni, Xinyi Li, Jun Pu, Jie Chen, Jian Zhang, Shaoyong Lu, Chuan Lv, Mingfei Ji
Summary: RAS is a key oncogenic protein, and mutations in it can lead to human cancer. Recent studies have identified several phosphorylation residues in RAS protein that can regulate its activity, providing a new direction for developing anti-RAS drugs. This review summarizes the research advances in RAS phosphorylation and provides insights into therapeutic strategies.
ACTA PHARMACEUTICA SINICA B
(2021)
Article
Endocrinology & Metabolism
Christopher S. Krumm, Renee S. Landzberg, Lavoisier Ramos-Espiritu, Carolina Adura, Xu Liu, Mariana Acuna, Yang Xie, Xu Xu, Matthew C. Tillman, Yingxia Li, J. Fraser Glickman, Eric A. Ortlund, John D. Ginn, David E. Cohen
Summary: Them1, a long chain acyl-CoA thioesterase, plays a regulatory role in energy metabolism and shows potential value in the treatment of NAFLD. The study identified two allosteric inhibitors that promoted fatty acid oxidation and reduced glucose production.
MOLECULAR METABOLISM
(2023)
Article
Multidisciplinary Sciences
Nora-Guadalupe P. Ramirez, Jeon Lee, Yue Zheng, Lianbo Li, Bryce Dennis, Didi Chen, Ashwini Challa, Vicente Planelles, Kenneth D. Westover, Neal M. Alto, Ivan D'Orso
Summary: This study revealed an undescribed modulator, ADAP1, that influences the fate of HIV-1 provirus. The experimental results showed that ADAP1 can enhance T cell signaling and facilitate the escape of latent HIV-1 by activating the ERK-AP-1 axis.
NATURE COMMUNICATIONS
(2022)
Article
Oncology
Danielle R. Cook, Melissa Kang, Timothy D. Martin, Joseph A. Galanko, Gabriela H. Loeza, Dimitri G. Trembath, Verline Justilien, Karen A. Pickering, David F. Vincent, Armin Jarosch, Philipp Jurmeister, Andrew M. Waters, Priya S. Hibshman, Andrew D. Campbell, Catriona A. Ford, Temitope O. Keku, Jen Jen Yeh, Michael S. Lee, Adrienne D. Cox, Alan P. Fields, Robert S. Sandler, Owen J. Sansom, Christine Sers, Antje Schaefer, Channing J. Der
Summary: In colorectal cancer, the overexpression and mislocalization of ECT2 support its role as an oncogenic driver gene independent of normal cell cytokinesis.
Article
Pharmacology & Pharmacy
Inge E. Krabbendam, Birgit Honrath, Laura Bothof, Eduardo Silva-Pavez, Hernan Huerta, Natalia M. Penaranda Fajardo, Frank Dekker, Martina Schmidt, Carsten Culmsee, Julio Cesar Cardenas, Frank Kruyt, Amalia M. Dolga
BIOCHEMICAL PHARMACOLOGY
(2020)
Review
Pharmacology & Pharmacy
Angelina Osipyan, Deng Chen, Frank J. Dekker
Summary: Epigenetic mechanisms play a crucial role in regulating tissue-specific expression of cytokine genes. MIF, a key cytokine involved in cancer and inflammation, triggers signaling pathways by binding to receptors like CD74. Abnormal expression of MIF and altered activity states of connected pathways are linked to inflammatory diseases and cancer. Therapeutic strategies based on epigenetic mechanisms have the potential to regulate MIF-mediated signaling in cancer and inflammation.
DRUG DISCOVERY TODAY
(2021)
Article
Chemistry, Analytical
Alienke van Pijkeren, Jorn Dietze, Alejandro Sanchez Brotons, Anna-Sophia Egger, Tim Lijster, Andrei Barcaru, Madlen Hotze, Philipp Kobler, Frank J. Dekker, Peter Horvatovich, Barbro N. Melgert, Mathias Ziegler, Kathrin Thedieck, Ines Heiland, Rainer Bischoff, Marcel Kwiatkowski
Summary: The study introduces a new approach, combining metabolic and chemical labeling, to accurately observe site-specific lysine acetylation dynamics. This method allows for the determination of reaction rates for acetylation and deacetylation.
ANALYTICAL CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Zhangping Xiao, Shanshan Song, Deng Chen, Ronald van Merkerk, Petra E. van Der Wouden, Robbert H. Cool, Wim J. Quax, Gerrit J. Poelarends, Barbro N. Melgert, Frank J. Dekker
Summary: The development of a MIF-targeted PROTAC, MD13, is able to induce MIF degradation at low concentrations and suppress the proliferation of inflammatory and cancer cells, demonstrating the potential therapeutic value of PROTACs in cancer treatment.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Multidisciplinary
Deng Chen, Zhangping Xiao, Hao Guo, Dea Gogishvili, Rita Setroikromo, Petra E. van der Wouden, Frank J. Dekker
Summary: Labelox B is a potent covalent LOX inhibitor that can efficiently label endogenous LOX in living cells, revealing the localization of LOX in the nucleus and its potential involvement in chromatin modifications.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Biochemistry & Molecular Biology
Martijn R. H. Zwinderman, Thamar Jessurun Lobo, Petra E. van der Wouden, Diana C. J. Spierings, Marcel A. T. M. van Vugt, Peter M. Lansdorp, Victor Guryev, Frank J. Dekker
Summary: This research reveals that newly synthesized chromatin proteins are preferentially deposited on DNA replicated by the lagging strand machinery. However, under replication stress or inhibition of specific kinases, this deposition bias is inverted to the strand replicated by the leading strand polymerase.
ACS CHEMICAL BIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Shanshan Song, Zhangping Xiao, Frank J. Dekker, Gerrit J. Poelarends, Barbro N. Melgert
Summary: The family of macrophage migration inhibitory factor (MIF) proteins in humans consists of MIF, D-dopachrome tautomerase (D-DT), and DDT-like (DDTL). MIF has various effects on cellular processes, while the functions of D-DT and DDTL are still unclear. Targeting MIF therapeutically should be carefully considered due to its multiple functions.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Chemistry, Multidisciplinary
Zhangping Xiao, Deng Chen, Fabian Mulder, Shanshan Song, Petra E. Wouden, Robbert H. Cool, Barbro N. Melgert, Gerrit J. Poelarends, Frank J. Dekker
Summary: This study reported the development and application of a new probe 8 for the selective labeling of macrophage migration inhibitory factor (MIF) and its homolog MIF2, facilitating research on their roles in cancer and other diseases.
CHEMISTRY-A EUROPEAN JOURNAL
(2022)
Article
Biochemical Research Methods
Frank Klont, Marcel Kwiatkowski, Alen Faiz, Thea van den Bosch, Simon D. Pouwels, Frank J. Dekker, Nick H. T. ten Hacken, Peter Horvatovich, Rainer Bischoff
Summary: This study discusses the use of adsorptive microtiter plates for protein enrichment prior to LC-MS detection, highlighting the potential usefulness of these plates in affinity purification workflows. Opportunities and challenges of corresponding workflows are explored based on both targeted and discovery-based experiments.
JOURNAL OF PROTEOME RESEARCH
(2021)
Article
Immunology
Jan G. T. Vogel, Joko P. Wibowo, Hillina Fan, Rita Setroikromo, Kan Wang, Alexander Domling, Frank J. Dekker, Wim J. Quax
Summary: This study successfully synthesized chromene-derived inhibitory molecules that competitively inhibit the acylase PvdQ, reducing the formation of pyoverdine in P. aeruginosa and demonstrating a protective effect in an infection model.
MICROBES AND INFECTION
(2022)
Review
Chemistry, Multidisciplinary
Piermichele Kobauri, Frank J. Dekker, Wiktor Szymanski, Ben L. Feringa
Summary: Photopharmacology is an attractive approach for targeted drug action using light, where molecular photoswitches are introduced into biologically active small molecules for optical control. This review categorizes photopharmacological efforts based on medicinal chemistry strategies, focusing on diffusible photochromic ligands modified with E-Z bond isomerization photoswitches. Photoswitchable ligands are often designed as analogs of existing compounds using various approaches. Through analyzing instructive examples, the state of the art and future opportunities for rational design in photopharmacology are discussed.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Chunlong Zhao, Shipeng Chen, Deng Chen, Claudia Rio-Berge, Jianqiu Zhang, Petra E. Van Der Wouden, Toos Daemen, Frank J. Dekker
Summary: The HDAC3-directed PROTAC P7 has anti-inflammatory activity and blocks macrophage polarization, demonstrating that this molecular mechanism can be targeted with small molecule therapeutics.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Biochemistry & Molecular Biology
Chunlong Zhao, Deng Chen, Fengzhi Suo, Rita Setroikromo, Wim J. Quax, Frank J. Dekker
Summary: Aberrations in HDAC8 functions are closely linked to various diseases, and development of HDAC8 degradation inducers may be more promising than HDAC8 inhibitors. Using the PROTAC strategy, we developed a selective and potent HDAC8 degradation inducer CT-4 with single-digit nano-molar DC50 values and over 95% Dmax in both MDA-MB-231 cells and T-cell leukemia cells. CT-4 showed potent anti-migration activity and limited anti-proliferative activity in MDA-MB-231 cells, while effectively inducing apoptotic cell death in Jurkat cells. These findings suggest that the development of HDAC8 degradation inducers holds great potential for the treatment of HDAC8-related diseases.
BIOORGANIC CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Chunlong Zhao, Frank J. Dekker
Summary: This review discusses the strategies and advantages and disadvantages of proteolysis targeting chimeras (PROTACs), focusing on enhancing their effectiveness and selectivity. The future perspectives for PROTAC design are also discussed.
ACS PHARMACOLOGY & TRANSLATIONAL SCIENCE
(2022)
Article
Chemistry, Multidisciplinary
Piermichele Kobauri, Wiktor Szymanski, Fangyuan Cao, Sebastian Thallmair, Siewert J. Marrink, Martin D. Witte, Frank J. Dekker, Ben L. Feringa
Summary: Biaryl sulfonamides are excellent candidates for the azologization approach, yielding photoswitchable drugs more active in their metastable cis state. The scope and limitations of this strategy for rational design in photopharmacology are discussed.
CHEMICAL COMMUNICATIONS
(2021)
