Article
Biochemistry & Molecular Biology
Su Wu, Gerhard Wagner
Summary: eIF4F plays diverse roles in human cancers, with overexpression of EIF4G1 being more selective than EIF4E, serving as a prognostic indicator in cancer patients. This expression imbalance affects housekeeping pathways and cancer-related pathways, leading to cap-independent initiation due to eIF4G1 hyperphosphorylation. These findings provide a novel model of dysregulated eIF4F function and highlight the clinical relevance of cap-(in)dependent initiation in cancer.
Article
Genetics & Heredity
Naotaka Ochi, Mai P. Nakamura, Rina Nagata, Naoki P. Wakasa, Ryosuke Nakano, Tatsushi P. Igaki
Summary: Cell competition is a context-dependent process where unfit cells are eliminated when confronted with fitter cells. Through genetic studies in Drosophila, it was found that ER stress leads to cell competition via upregulation of the bZIP transcription factor Xrp1, leading to reduced protein synthesis and cell death. These findings suggest that Xrp1-mediated phosphorylation of eIF2 alpha could be a common mechanism of cell competition triggered by different stimuli.
Article
Agriculture, Dairy & Animal Science
Yanli Zhao, Xiaoyu Guo, Sumei Yan, Binlin Shi, Ran Sheng
Summary: The study revealed that acetate regulates milk fat synthesis through the mTOR/eIF4E signaling pathway, promoting fatty acid synthesis and TG accumulation, while rapamycin and silencing eIF4E can inhibit this positive effect.
JOURNAL OF DAIRY SCIENCE
(2021)
Article
Oncology
Dexter Kai Hao Thng, Lissa Hooi, Clarissa Chin Min Toh, Jhin Jieh Lim, Deepa Rajagopalan, Imran Qamar Charles Syariff, Zher Min Tan, Masturah Bte Mohd Abdul Rashid, Lei Zhou, Alfred Wei Chieh Kow, Glenn Kunnath Bonney, Brian Kim Poh Goh, Juinn Huar Kam, Sudhakar Jha, Yock Young Dan, Pierce Kah Hoe Chow, Tan Boon Toh, Edward Kai-Hua Chow
Summary: Hepatocellular carcinoma (HCC) is a highly lethal cancer with high prevalence worldwide. In this study, we demonstrated the overexpression of histone methyltransferase G9a in HCC, particularly in Myc-driven liver tumors. The increased expression of G9a was associated with poor prognosis and lower survival rates in HCC patients. We also revealed the cooperative interaction between c-Myc and G9a in HCC, highlighting their role in gene repression and cancer development. Additionally, combination therapy targeting G9a and CDK9 showed promising efficacy in patient-derived models of Myc-driven HCC.
MOLECULAR ONCOLOGY
(2023)
Article
Engineering, Biomedical
Qing Zhang, Mengyu Xin, Shuang Yang, Qiuyu Wu, Xi Xiang, Tianqi Wang, Wen Zhong, Marco N. Helder, Richard T. Jaspers, Janak Lal Pathak, Yin Xiao
Summary: Targeting macrophages to regulate the immune microenvironment is a new strategy for bone regeneration with nano-drugs. Nano-drugs have achieved surprising anti-inflammatory and bone-regenerative effects, however, their underlying mechanisms in macrophages remain to be clarified.
MATERIALS TODAY BIO
(2023)
Article
Neurosciences
Marta Garcia-Juan, Lara Ordonez-Gutierrez, Francisco Wandosell
Summary: This study found that modulation of autophagy in astrocytes can affect the generation and degradation of beta-amyloid, which is associated with neurodegenerative diseases like Alzheimer's disease. While the inhibition of MTORC1 reduced beta-amyloid secretion through moderate autophagy induction, increased activity of AMPK had different effects on beta-amyloid secretion. These findings suggest that AMPK plays a significantly different role in astrocytes compared to other cell types.
Article
Endocrinology & Metabolism
Sangam Rajak, Sherwin Xie, Archana Tewari, Sana Raza, Yajun Wu, Boon-Huat Bay, Paul M. Yen, Rohit A. Sinha
Summary: This study identified a novel crinophagic mechanism regulated by MTORC1 signaling for intracellular turnover of glucagon in pancreatic alpha cells.
MOLECULAR METABOLISM
(2021)
Article
Biochemistry & Molecular Biology
Shu-Ting Hung, Gabriel R. Linares, Wen-Hsuan Chang, Yunsun Eoh, Gopinath Krishnan, Stacee Mendonca, Sarah Hong, Yingxiao Shi, Manuel Santana, Chuol Kueth, Samantha Macklin-Isquierdo, Sarah Perry, Sarah Duhaime, Claudia Maios, Jonathan Chang, Joscany Perez, Alexander Couto, Jesse Lai, Yichen Li, Samuel Alworth, Eric Hendricks, Yaoming Wang, Berislav Zlokovic, Dion K. Dickman, J. Alex Parker, Daniela C. Zarnescu, Fen-Biao Gao, Justin K. Ichida
Summary: Amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disease, has diverse genetic causes. Pharmacological inhibition of PIKFYVE kinase can activate an unconventional protein clearance mechanism, improving ALS pathology and extending survival in animal models and patient-derived motor neurons representing different forms of ALS.
Article
Immunology
Mark R. Silvis, Dilru Silva, Riley Rohweder, Sophia Schuman, Swapna Gudipaty, Amanda Truong, Jeffrey Yap, Kajsa Affolter, Martin McMahon, Conan Kinsey
Summary: Pharmacological inhibition of KRAS>RAF>MEK1/2>ERK1/2 signaling does not benefit patients with pancreatic ductal adenocarcinoma (PDAC). However, combining MEK1/2 inhibition with autophagy inhibition shows anti-tumor effects. Resistance to the treatment is associated with c-MYC gene amplification, which can be overcome by using a CDK4/6 inhibitor along with chloroquine or hydroxychloroquine.
JOURNAL OF EXPERIMENTAL MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Yang Chen, Zhenzhen Wang, Xuemei Xian, Yun Zhuang, Jiajia Chang, Xiaoqiang Zhan, Xufeng Han, Quangang Chen, Zhangping Yang, Renjin Chen
Summary: Atherosclerosis, a chronic inflammatory disease, may be reduced by inhibiting Fasn and lipid metabolism in macrophages through Eif6 deficiency.
Article
Biochemistry & Molecular Biology
Weijing Yao, Yuting Chen, Yingcong Chen, Pengwei Zhao, Jing Liu, Yi Zhang, Qiang Jiang, Choufei Wu, Yu Xie, Siyu Fan, Miao Ye, Yigang Wang, Yuyao Feng, Xue Bai, Mingzhu Fan, Shan Feng, Juan Wang, Yixian Cui, Hongguang Xia, Cheng Ma, Zhiping Xie, Liqin Zhang, Qiming Sun, Wei Liu, Cong Yi
Summary: In this study, the direct interaction between Rab GTPase Ypt1/Rab1 and Atg23 and Atg17 was found to be crucial for the stepwise assembly of autophagy initiation complexes. Additionally, the phosphorylation of Ypt1 by TOR was shown to regulate the assembly of ATG proteins during autophagy initiation. Therefore, TOR-mediated Ypt1 is proposed as a multifunctional assembly factor that controls autophagy initiation by regulating the stepwise assembly of ATG proteins.
Article
Biochemistry & Molecular Biology
Weijing Yao, Yuting Chen, Yingcong Chen, Pengwei Zhao, Jing Liu, Yi Zhang, Qiang Jiang, Choufei Wu, Yu Xie, Siyu Fan, Miao Ye, Yigang Wang, Yuyao Feng, Xue Bai, Mingzhu Fan, Shan Feng, Juan Wang, Yixian Cui, Hongguang Xia, Cheng Ma, Zhiping Xie, Liqin Zhang, Qiming Sun, Wei Liu, Cong Yi
Summary: The Rab GTPase Ypt1/Rab1 is identified as an essential regulator in autophagy, and its binding partners Atg23 and Atg17 play important roles in the stepwise assembly of autophagy initiation complexes. Furthermore, TOR phosphorylates Ypt1 to control autophagy initiation.
Article
Pharmacology & Pharmacy
Martina P. Morawe, Fan Liao, Willi Amberg, Jeroen van Bergeijk, Rui Chang, Mary Gulino, Caitlin Hamilton, Carolin Hoft, Casey Lumpkin, Bryan Mastis, Emily McGlame, Judith Nuber, Christian Plaas, Brinda Ravikumar, Kaushambi Roy, Marion Schanzenbaecher, Joseph Tierno, Viktor Lakics, Tammy Dellovade, Matthew Townsend
Summary: In this study, the researchers aimed to reduce tau pathology in Alzheimer's Disease by activating mTOR-dependent autophagy. They found that mTOR inhibitors could effectively reduce tau pathology, with PQR530 showing better results even when treatment was started after the onset of pathology. The researchers concluded that intermittent dosing of mTOR inhibitors can have a disease-modifying effect in AD.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Suhrid Banskota, Huaqing Wang, Yun Han Kwon, Jaya Gautam, Sabah Haq, Jensine Grondin, Gregory R. Steinberg, Waliul I. Khan
Summary: Inhibiting NOX2 can alleviate colitis independently of AMPK, as shown by the study.
Article
Biochemistry & Molecular Biology
Qingyu Zhou, James D. Quirk, Ying Hu, Huimin Yan, Joseph P. Gaut, Christine T. N. Pham, Samuel A. Wickline, Hua Pan
Summary: Researchers have discovered that using rapamycin-loaded perfluorocarbon nanoparticles (PFC NP) can effectively deliver the drug to the injured kidneys, mitigating cisplatin-induced acute kidney injury and preserving renal function.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biology
Whitney L. Johnson, William T. Yewdell, Jason C. Bell, Shannon M. McNulty, Zachary Duda, Rachel J. O'Neill, Beth A. Sullivan, Aaron F. Straight
Article
Biochemistry & Molecular Biology
Shannon M. McNulty, Beth A. Sullivan
CHROMOSOME RESEARCH
(2018)
Editorial Material
Cell Biology
Shannon M. McNulty, Beth A. Sullivan
JOURNAL OF CELL BIOLOGY
(2019)
Editorial Material
Cell Biology
Beth A. Sullivan
DEVELOPMENTAL CELL
(2020)
Article
Oncology
Lori L. Sullivan, Beth A. Sullivan
EXPERIMENTAL CELL RESEARCH
(2020)
Editorial Material
Biochemistry & Molecular Biology
Beth A. Sullivan
CHROMOSOME RESEARCH
(2020)
Article
Multidisciplinary Sciences
Karen H. Miga, Sergey Koren, Arang Rhie, Mitchell R. Vollger, Ariel Gershman, Andrey Bzikadze, Shelise Brooks, Edmund Howe, David Porubsky, Glennis A. Logsdon, Valerie A. Schneider, Tamara Potapova, Jonathan Wood, William Chow, Joel Armstrong, Jeanne Fredrickson, Evgenia Pak, Kristof Tigyi, Milinn Kremitzki, Christopher Markovic, Valerie Maduro, Amalia Dutra, Gerard G. Bouffard, Alexander M. Chang, Nancy F. Hansen, Amy B. Wilfert, Francoise Thibaud-Nissen, Anthony D. Schmitt, Jon-Matthew Belton, Siddarth Selvaraj, Megan Y. Dennis, Daniela C. Soto, Ruta Sahasrabudhe, Gulhan Kaya, Josh Quick, Nicholas J. Loman, Nadine Holmes, Matthew Loose, Urvashi Surti, Rosa Ana Risques, Tina A. Graves Lindsay, Robert Fulton, Ira Hall, Benedict Paten, Kerstin Howe, Winston Timp, Alice Young, James C. Mullikin, Pavel A. Pevzner, Jennifer L. Gerton, Beth A. Sullivan, Evan E. Eichler, Adam M. Phillippy
Article
Biochemistry & Molecular Biology
Sebastian Hoffmann, Helena M. Izquierdo, Riccardo Gamba, Florian Chardon, Marie Dumont, Veer Keizer, Solene Herve, Shannon M. McNulty, Beth A. Sullivan, Nicolas Manel, Daniele Fachinetti
Editorial Material
Biochemistry & Molecular Biology
Beth A. Sullivan
CHROMOSOME RESEARCH
(2021)
Review
Genetics & Heredity
Evon M. DeBose-Scarlett, Beth A. Sullivan
Summary: Centromeres are crucial for genome inheritance, with abnormal function linked to various diseases. Ectopic centromeres can form at new genomic locations, impacting genome stability and disease development. While certain genome regions influence neocentromere activation, the universal mechanism remains unclear.
ANNUAL REVIEW OF GENETICS, VOL 55
(2021)
Review
Biochemistry & Molecular Biology
Karen H. Miga, Beth A. Sullivan
Summary: The recent completion of a comprehensive human genome project has provided new insights into the complexity of genome structure and function, leading to a deeper understanding of genome organization and function. This will help in accurate diagnosis of human diseases, improvement of treatment methods, and advancement of future preventive medicine and healthcare.
HUMAN MOLECULAR GENETICS
(2021)
Article
Multidisciplinary Sciences
Nicolas Altemose, Glennis A. Logsdon, Andrey Bzikadze, Pragya Sidhwani, Sasha A. Langley, Gina Caldas, Savannah J. Hoyt, Lev Uralsky, Fedor D. Ryabov, Colin J. Shew, Michael E. G. Sauria, Matthew Borchers, Ariel Gershman, Alla Mikheenko, Valery A. Shepelev, Tatiana Dvorkina, Olga Kunyavskaya, Mitchell R. Vollger, Arang Rhie, Ann M. McCartney, Mobin Asri, Ryan Lorig-Roach, Kishwar Shafin, Julian K. Lucas, Sergey Aganezov, Daniel Olson, Leonardo Gomes de Lima, Tamara Potapova, Gabrielle A. Hartley, Marina Haukness, Peter Kerpedjiev, Fedor Gusev, Kristof Tigyi, Shelise Brooks, Alice Young, Sergey Nurk, Sergey Koren, Sofie R. Salama, Benedict Paten, Evgeny Rogaev, Aaron Streets, Gary H. Karpen, Abby F. Dernburg, Beth A. Sullivan, Aaron F. Straight, Travis J. Wheeler, Jennifer L. Gerton, Evan E. Eichler, Adam M. Phillippy, Winston Timp, Megan Y. Dennis, Rachel J. O'Neill, Justin M. Zook, Michael C. Schatz, Pavel A. Pevzner, Mark Diekhans, Charles H. Langley, Ivan A. Alexandrov, Karen H. Miga
Summary: Current human genome assemblies have neglected repetitive sequences near centromeres, hindering our understanding of their organization and evolution. A new approach has allowed researchers to comprehensively study these sequences, revealing their structural rearrangements and variations.
Article
Biology
Peter A. Larsen, R. Alan Harris, Yue Liu, Shwetha C. Murali, C. Ryan Campbell, Adam D. Brown, Beth A. Sullivan, Jennifer Shelton, Susan J. Brown, Muthuswamy Raveendran, Olga Dudchenko, Ido Machol, Neva C. Durand, Muhammad S. Shamim, Erez Lieberman Aiden, Donna M. Muzny, Richard A. Gibbs, Anne D. Yoder, Jeffrey Rogers, Kim C. Worley
Article
Biochemistry & Molecular Biology
Aiko Iwata-Otsubo, Jennine M. Dawicki-McKenna, Takashi Akera, Samantha J. Falk, Lukas Chmatal, Karren Yang, Beth A. Sullivan, Richard M. Schultz, Michael A. Lampson, Ben E. Black
Article
Cell Biology
Shannon M. McNulty, Lori L. Sullivan, Beth A. Sullivan
DEVELOPMENTAL CELL
(2017)