Review
Biochemistry & Molecular Biology
Patricia Ramos-Ramirez, Omar Tliba
Summary: This passage discusses how glucocorticoids act through the GR receptor to produce different cellular responses throughout the body and the different effects of GRα and GRβ on the human body.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Medicinal
Timothy R. Stachowski, Marcus Fischer
Summary: Protein flexibility is crucial in drug design, especially for targeting dynamic proteins like Hsp90. The analysis of Hsp90 alpha crystal structures revealed different conformations of the lid domain that accommodate chemically distinct ligands. This study highlights the importance of considering protein ensembles and warns against overinterpreting individual crystal structures in drug design.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Qiwei Jiang, Xiaomei Zhang, Xiaoming Dai, Shiyao Han, Xueji Wu, Lei Wang, Wenyi Wei, Ning Zhang, Wei Xie, Jianping Guo
Summary: The study demonstrates that S6K1 can directly phosphorylate PDK1, inhibiting the activity of AKT kinase and its role in tumorigenesis. This feedback regulation of AKT signaling through S6K1-mediated PDK1 phosphorylation provides insight into the regulation of the AKT pathway and potential strategies for combating mutant PDK1-driven cancers.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Mahamat Babagana, Lorin R. Brown, Hannah Z. Slabodkin, Julia V. Kichina, Eugene S. Kandel
Summary: Hyperactivity of AKT in cancer cells leads to increased sensitivity to proteotoxic stress, manifested by heightened response to heat shock and greater dependence on XBP1 for growth. This stress-induced vulnerability can be exploited for therapeutic targeting.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Sofia Fertuzinhos, Emilie Legue, Davis Li, Karel F. Liem
Summary: This study reveals the impact of Tubb4a gene mutation on brain neurons and myelination, and demonstrates the association of cell-autonomous cell death with the enrichment of mutant protein in specific cell types. Furthermore, the study identifies the compensatory transcriptional up-regulation of related tubulin genes to compensate for the loss of Tubb4a function.
Article
Chemistry, Medicinal
Xiaoli Li, Guoli Wang, Xiaolin Zhou, Huijie Zhao, Xiaojie Chen, Qixiao Cui, Minjing Li, Xihang Gao, Xiaoyu Wei, Lei Ye, Defang Li, Pan Hong
Summary: In this study, it was found that the compound PPP extracted from Dysosma versipellis inhibits the proliferation of gastric cancer cells by blocking the AKT/mTOR signaling pathway and inducing apoptosis. It also suppresses tumor growth in vivo and may target heat shock protein 90 (HSP90) to disrupt its binding to AKT.
PHYTOTHERAPY RESEARCH
(2023)
Article
Chemistry, Physical
Angeliki Giannoulis, Akiva Feintuch, Tamar Unger, Shiran Amir, Daniella Goldfarb
Summary: This study explored the binding of co-chaperone Sbal to yeast Hsp90 (yHsp90) and the conformational change of yHsp90 in the pre- and post-ATP hydrolysis states using DEER distance measurements. The results showed that Sba1 can induce a closed conformation in yHsp90, providing structural experimental evidence for the tuning of yHsp90 conformation by Sba1 binding.
JOURNAL OF PHYSICAL CHEMISTRY LETTERS
(2021)
Article
Environmental Sciences
Chien-Chang Kao, Yi-Ching Cheng, Ming-Hsin Yang, Tai-Lung Cha, Guang-Huan Sun, Chi-Tang Ho, Ying-Chao Lin, Hao-Kuang Wang, Sheng-Tang Wu, Tzong-Der Way
Summary: Curcuminoids have shown inhibitory effects on HER2-overexpressing bladder cancer cells, and can be used in combination with chemotherapeutic agents to exhibit additive activity, indicating their potential as a new candidate for anti-tumor drug development.
ENVIRONMENTAL TOXICOLOGY
(2021)
Article
Cell Biology
Xuehui Wang, Hongming Song, Lin Fang, Tianqi Wu
Summary: In this study, it was found that circPRKCI, derived from the PRKCI gene, was highly expressed in TNBC and could promote the proliferation and migration of TNBC by regulating the WBP2 and PI3K/AKT signaling pathway, providing a new avenue for TNBC therapy.
CELL DEATH DISCOVERY
(2022)
Article
Biochemistry & Molecular Biology
Xin Tang, Cheng Chang, Daniel Mosallaei, David T. Woodley, Axel H. Schonthal, Mei Chen, Wei Li
Summary: The expression of Hsp90 varies dramatically among different types of noncancer cells and organs, which affects the sensitivity and resistance to Hsp90 ATP-binding inhibitors. Even in the presence of full Hsp90 alpha, a minimum amount of Hsp90 beta is still required for cell growth and survival. These findings could complicate biomarker selection, toxicity readout, and clinical efficacy of Hsp90-ATP-binding inhibitors in cancer clinical trials.
MOLECULAR AND CELLULAR BIOLOGY
(2022)
Article
Pharmacology & Pharmacy
Li Yuan-Ce, Zhang Qi, Zhang Hong-Yang, Wang Yan-Wen, Sun Yu-Mei, Yang Bi-Juan, Yin Jun-Lin
Summary: Artesunate inhibits tumor cell proliferation by targeting Hsp90 and has potential as a novel anti-tumor drug.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Jie Zeng, Si-Li He, Li-Jie Li, Chen Wang
Summary: The study found that Hsp90 expression is up-regulated in HPV16(+) cervical cancer tissues and cells, and knockdown of Hsp90 inhibited the proliferation and migration of cervical cancer cells. PD-L1 expression in cervical cancer tissues was positively correlated with Hsp90 expression, and Hsp90 regulated PD-L1 expression via the HER2/PI3K/AKT signaling pathway. The results suggest that Hsp90 knockdown has therapeutic potential in treating HPV16(+) cervical cancers.
MOLECULAR MEDICINE
(2021)
Article
Cell Biology
Kaiming Cao, Shixuan Li, Yu Wang, Hongze Hu, Sijia Xiang, Qianling Zhang, Yangzhong Liu
Summary: Recently, it has been discovered that bacterial cells contain membrane-less organelles formed by liquid-liquid phase separation of proteins or nucleic acids. In this study, it was found that the bacterial nickel-responsive regulatory protein, NikR, exhibits liquid-liquid phase separation in both solution and cells. Furthermore, disrupting the phase separation promotes the expression of nickel transporter genes, suggesting that the formation of these membrane-less compartments is a regulatory mechanism in bacterial cells.
Article
Chemistry, Medicinal
Taylor Merfeld, Shuxia Peng, Bradley M. Keegan, Vincent M. Crowley, Christopher M. Brackett, Andrew Gutierrez, Nathan R. McCann, Tyelor S. Reynolds, Matthew C. Rhodes, Katherine M. Byrd, Junpeng Deng, Robert L. Matts, Brian S. J. Blagg
Summary: Hsp90 isoform-selective inhibitors have specific cellular localization, function, and client proteins, making them a new paradigm for anti-cancer drugs. The mitochondrial isoform TRAP1, which is least understood, has been studied using novel TRAP1-selective inhibitors and co-crystal structures. Compound 36 was found to be a highly selective inhibitor of TRAP1 and exhibited various effects such as client protein degradation, disruption of mitochondrial function, and alteration of cellular metabolism.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Pathology
Fang Deng, Yaguang Weng, Xian Li, Teng Wang, Mengtian Fan, Qiong Shi
Summary: IL-8 plays a crucial role in the progression of TNBC, promoting tumor cell migration and growth, affecting cell cycle, and influencing the expression of certain cell cycle proteins.
PATHOLOGY RESEARCH AND PRACTICE
(2021)
Article
Medicine, Research & Experimental
Wenquan Hu, Zhong Liu, Valerie Salato, Paula E. North, Joyce Bischoff, Suresh N. Kumar, Zhi Fang, Sujith Rajan, M. Mahmood Hussain, Qing R. Miao
Summary: Infantile hemangioma is characterized by rapid growth and slow involution of disorganized blood vessels. NGBR was found to be highly expressed in the proliferating phase of hemangioma but decreased in the involuting phase. Knockdown of NGBR in HemSCs attenuated RAS activation and inhibited cell migration and proliferation, suggesting its role in controlling growth and differentiation of hemangioma stem cells.
Article
Genetics & Heredity
Carolina Courage, Karen L. Oliver, Eon Joo Park, Jillian M. Cameron, Kariona A. Grabinska, Mikko Muona, Laura Canafoglia, Antonio Gambardella, Edith Said, Zaid Afawi, Betul Baykan, Christian Brandt, Carlo di Bonaventura, Hui Bein Chew, Chiara Criscuolo, Leanne M. Dibbens, Barbara Castellotti, Patrizia Riguzzi, Angelo Labate, Alessandro Filla, Anna T. Giallonardo, Geza Berecki, Christopher B. Jackson, Tarja Joensuu, John A. Damiano, Sara Kivity, Amos Korczyn, Aarno Palotie, Pasquale Striano, Davide Uccellini, Loretta Giuliano, Eva Andermann, Ingrid E. Scheffer, Roberto Michelucci, Melanie Bahlo, Silvana Franceschetti, William C. Sessa, Samuel F. Berkovic, Anna-Elina Lehesjoki
Summary: Progressive myoclonus epilepsies (PMEs) are a group of clinically and genetically heterogeneous rare diseases, with over 70% of cases now molecularly solved. By performing whole-exome sequencing on unsolved PME-affected individuals, novel disease-causing variants were identified, particularly in cases studied with additional family members. A variety of new genes related to lysosomal and endosomal function were discovered, shedding light on the genetic complexity of PME.
AMERICAN JOURNAL OF HUMAN GENETICS
(2021)
Article
Biology
Takeshi Ninchoji, Dominic T. Love, Ross O. Smith, Marie Hedlund, Dietmar Vestweber, William C. Sessa, Lena Claesson-Welsh
Summary: In this study, suppression of nitric oxide formation resulted in reduced retinal neoangiogenesis and decreased vascular leakage through stabilized endothelial adherens junctions. This has important implications for preventing vascular leakage in ocular diseases.
Article
Ophthalmology
Pascal N. Bernatchez, Bo Tao, Ralph A. Bradshaw, David Eveleth, William C. Sessa
Summary: The study aimed to identify a novel CPP for improved delivery of a truncated Cav modulator. Results showed that fusion with peptide RRPPR efficiently blocked NO release and VEGF-induced permeability, reducing immune-mediated retinal damage.
TRANSLATIONAL VISION SCIENCE & TECHNOLOGY
(2021)
Article
Cardiac & Cardiovascular Systems
Hyojin Park, Jessica Furtado, Mathilde Poulet, Minhwan Chung, Sanguk Yun, Sungwoon Lee, William C. Sessa, Claudio A. Franco, Martin A. Schwartz, Anne Eichmann
Summary: This study demonstrates the critical role of ALK1 in controlling endothelial cell polarization against blood flow direction and promoting vein-to-artery migration, while identifying integrin-YAP/TAZ signaling blockers as potential targets for preventing vascular malformations in patients with hereditary hemorrhagic telangiectasia.
Article
Biology
Joseph Wayne M. Fowler, Rong Zhang, Bo Tao, Nabil E. Boutagy, William C. Sessa
Summary: The relationship between cholesterol homeostasis and immunity in leukocytes has been extensively studied, but not much is known about this relationship in vascular endothelium cells. This study reveals the role of cholesterol and the transcription regulator SREBP2 in the inflammatory response of endothelial cells.
Article
Biotechnology & Applied Microbiology
Chang Liu, Sijie Li, Xiaoxiao Zhang, Chunxiang Jin, Baofeng Zhao, Liying Li, Qing Robert Miao, Ying Jin, Zhimin Fan
Summary: NgBR plays a role in regulating metabolism and paclitaxel resistance in breast cancer, and may be a new therapeutic target for improving chemoresistance in ER-positive breast cancer.
CANCER GENE THERAPY
(2023)
Correction
Biotechnology & Applied Microbiology
Chang Liu, Sijie Li, Xiaoxiao Zhang, Chunxiang Jin, Baofeng Zhao, Liying Li, Qing Robert Miao, Ying Jin, Zhimin Fan
CANCER GENE THERAPY
(2023)
Article
Biochemistry & Molecular Biology
Joseph Wayne M. Fowler, Nabil E. Boutagy, Rong Zhang, Daiki Horikami, Michael B. Whalen, Casey E. Romanoski, William C. Sessa
Summary: The transcription factor SREBP2 is the main regulator of cholesterol homeostasis and has been implicated in leukocyte immune responses. In this study, the role of SREBP2 in endothelial cells was investigated, revealing its impact on inflammatory chemokine production and interferon response genes.
JOURNAL OF LIPID RESEARCH
(2023)
Article
Multidisciplinary Sciences
Wenping Zhou, Wenxue Li, Shisheng Wang, Barbora Salovska, Zhenyi Hu, Bo Tao, Yi Di, Ujwal Punyamurtula, Benjamin E. E. Turk, William C. C. Sessa, Yansheng Liu
Summary: The authors used optogenetics and mass spectrometry-based phosphoproteomics to study the effects of different intensities, durations, and patterns of Akt1 activation on phosphorylation circuits, revealing downstream signaling outcomes of Akt1. The study showed that different intensities, durations, and patterns of Akt1 activation lead to distinct phosphorylation profiles in vascular endothelial cells, and also revealed the interaction between Akt1 signaling and growth factor signaling in these cells. The resulting dataset provides an important resource for future studies on AKT signaling and dynamics.
NATURE COMMUNICATIONS
(2023)
Review
Gastroenterology & Hepatology
Michele A. Rodrigues, Dawidson A. Gomes, Romina Fiorotto, Mateus T. Guerra, Jittima Weerachayaphorn, Tao Bo, William C. Sessa, Mario Strazzabosco, Michael H. Nathanson
Summary: Fluid and bicarbonate secretion in cholangiocytes is regulated by ITPR3, which localizes to the apical region. This localization is dependent on intact lipid rafts and interactions with CAV1 and MYH9. Disruption of lipid rafts or knockdown of CAV1 or MYH9 impairs ITPR3 localization and secretion.
HEPATOLOGY COMMUNICATIONS
(2022)
Article
Medicine, Research & Experimental
Zhi Fang, Xiaoran Sun, Xiang Wang, Ji Ma, Thomas Palaia, Ujala Rana, Benjamin Miao, Louis Ragolia, Wenquan Hu, Qing Robert Miao
Summary: The loss of cerebral cavernous malformation (CCM) genes leads to vascular lesions in the brain. This study reveals that genetic depletion of the NOGOB receptor (NGBR) in endothelial cells (ECs) results in CCM1/2 expression deficiency and cerebrovascular lesions. Mechanistically, NGBR is required for maintaining the expression of CCM1/2 in ECs through HBO1-mediated histone acetylation.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Review
Medicine, Research & Experimental
Nabil E. Boutagy, Abhishek K. Singh, William C. Sessa
Summary: Obesity is a major contributor to insulin resistance and type 2 diabetes, increasing the risk of cardiovascular disease. Metabolic changes caused by obesity negatively affect the vasculature, exacerbating disease progression. Understanding the cellular and molecular processes is crucial for optimizing medical therapies.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Article
Medicine, Research & Experimental
Ainara G. Cabodevilla, Songtao Tang, Sungwoon Lee, Adam E. Mullick, Jose O. Aleman, M. Mahmood Hussain, William C. Sessa, Nada A. Abumrad, Ira J. Goldberg
Summary: Despite the primary role of LpL in tissue uptake of fatty acids from chylomicrons, studies have shown that an additional pathway exists for transferring dietary lipids to tissues. This pathway involves endothelial cell uptake of chylomicrons, hydrolysis in lysosomes, and subsequent lipid accumulation in cells. Competing with HDL and targeting the scavenger receptor-BI can inhibit this process in vivo, potentially reducing lipid accumulation in tissues and preventing conditions such as eruptive xanthomas.
JOURNAL OF CLINICAL INVESTIGATION
(2021)
Article
Cell Biology
Qianying Yuan, Abdul Basit, Wenhua Liang, Rihao Qu, Yi Luan, Chunguang Ren, Ao Li, Xin Xu, Xiaoqing Liu, Chun Yang, Andrew Kuo, Richard Pierce, Longbo Zhang, Benjamin Turk, Xin Hu, Fangyong Li, Weixue Cui, Run Li, Danxia Huang, Lili Mo, William C. Sessa, Patty J. Lee, Yuval Kluger, Bing Su, Wenwen Tang, Jianxing He, Dianqing Wu
Summary: Pazopanib ameliorates ALI manifestations by inhibiting the phosphorylation of NADPH oxidase 2 subunit p47(phox) through MAP3K2 and MAP3K3. This drug also reduces edema in human lung transplantation recipients, indicating potential for treating ALI.
SCIENCE TRANSLATIONAL MEDICINE
(2021)