Article
Biochemistry & Molecular Biology
Ibrahim M. Sabbarini, Dvir Reif, Alexander J. McQuown, Anjali R. Nelliat, Jeffrey Prince, Britnie Santiago Membreno, Colin Chih-Chien Wu, Andrew W. Murray, Vladimir Denic
Summary: The conserved regulon of heat shock factor 1 in budding yeast contains chaperones for general protein folding as well as zinc-finger protein Zpr1, whose essential role in archaea and eukaryotes remains unknown. Here, we show that Zpr1 depletion causes acute proteotoxicity driven by biosynthesis of misfolded eukaryotic translation elongation factor 1A (eEF1A). Prolonged Zpr1 depletion leads to eEF1A insufficiency, thereby inducing the integrated stress response and inhibiting protein synthesis. Strikingly, we show by using two distinct biochemical reconstitution approaches that Zpr1 enables eEF1A to achieve a conformational state resistant to protease digestion. Lastly, we use a ColabFold model of the Zpr1-eEF1A complex to reveal a folding mechanism mediated by the Zpr1's zinc-finger and alpha-helical hairpin structures. Our work uncovers the long-sought-after function of Zpr1 as a bespoke chaperone tailored to the biogenesis of one of the most abundant proteins in the cell.
Article
Cell Biology
Toshio Kanno, Takahiro Nakajima, Yusuke Kawashima, Satoru Yokoyama, Hikari K. Asou, Shigemi Sasamoto, Koji Hayashizaki, Yuki Kinjo, Osamu Ohara, Toshinori Nakayama, Yusuke Endo
Summary: Treg cells play a critical role in immune regulation, relying on mitochondrial metabolism with Acsbg1 serving as a metabolic checkpoint. Exogenous supplementation of oleoyl-CoA can restore Treg cell function in the absence of Acsbg1, enhancing immunosuppressive capacity. This study highlights the importance of Acsbg1 in metabolic regulation of Treg cells.
Article
Plant Sciences
Xiaona Cui, Kaili Gao, Linjuan Wang, Mengyang Lv, Ziwen Li, Donghua Zheng, Wenwu Wu, Wen Yao, Liying Ding, Xiao Li, Jian-Kang Zhu, Hairong Zhang
Summary: AtGCN1 plays a crucial role in gene expression and translation in Arabidopsis, affecting flower development, seed growth, and various physiological processes.
FRONTIERS IN PLANT SCIENCE
(2021)
Article
Immunology
Quentin Philippot, Masato Ogishi, Jonathan Bohlen, Julia Puchan, Andres Augusto Arias, Tina Nguyen, Marta Martin-Fernandez, Clement Conil, Darawan Rinchai, Mana Momenilandi, Seyed Alireza Mandaviani, Mohammad Keramatipour, Jeremie Rosain, Rui Yang, Taushif Khan, Anna-Lena Neehus, Marie Materna, Ji Eun Han, Jessica Peel, Federico Mele, Marc Weisshaar, Sandra Jovic, Paul Bastard, Romain Levy, Tom Le Voyer, Peng Zhang, Majistor Raj Luxman Maglorius Renkilaraj, Carlos A. Arango-Franco, Simon Pelham, Yoann Seeleuthner, Mathieu Pochon, Manar Mahmoud Ahmad Ata, Fatima Al Ali, Melanie Migaud, Camille Soudee, Tatiana Kochetkov, Anne Molitor, Raphael Carapito, Seiamak Bahram, Bertrand Boisson, Claire Fieschi, Davood Mansouri, Nico Marr, Satoshi Okada, Mohammad Shahrooei, Nima Parvaneh, Zahra Chavoshzadeh, Aurelie Cobat, Dusan Bogunovic, Laurent Abel, Stuart G. Tangye, Cindy S. Ma, Vivien Beziat, Federica Sallusto, Stephanie Boisson-Dupuis, Jacinta Bustamante, Jean-Laurent Casanova, Anne Puel
Summary: Patients with IL-23R deficiency may suffer from Mendelian susceptibility to mycobacterial disease and chronic mucocutaneous candidiasis. IL-23 is essential for the production of IL-17A in MATT cells and for the production of IFN-y in both V62+ y6 T cells and MATT cells.
SCIENCE IMMUNOLOGY
(2023)
Article
Endocrinology & Metabolism
Hina Kosakamoto, Naoki Okamoto, Hide Aikawa, Yuki Sugiura, Makoto Suematsu, Ryusuke Niwa, Masayuki Miura, Fumiaki Obata
Summary: This study found that the non-essential amino acid tyrosine regulates the adaptive response to protein restriction in Drosophila by modulating ATF4 activity. Tyrosine induces the expression of ATF4 target genes in the fat body, leading to reduced protein synthesis and mTORC1 activity, and increased food intake.
Editorial Material
Cell Biology
Lucia Sedlackova, Tetsushi Kataura, Sovan Sarkar, Viktor I. Korolchuk
Summary: Age-related human pathologies present with a multitude of molecular and metabolic phenotypes, which contribute to tissue degeneration. Lack of understanding of the interdependence of these molecular pathologies limits therapeutic intervention strategies. In this study, we investigate the molecular events underlying cellular viability loss in autophagy deficiency associated with aging and age-related disease. We discover a novel axis linking autophagy and a metabolite, NAD, which mediates cellular demise. By elucidating the steps from mitochondrial recycling to NAD maintenance, we identify targets for therapeutic interventions in autophagy dysfunction.
Article
Nutrition & Dietetics
Han Fang, Kirsten P. Stone, Sujoy Ghosh, Laura A. Forney, Landon C. Sims, LeighAnn Vincik, Thomas W. Gettys
Summary: The primary sensing of dietary methionine restriction (MR) occurs in the liver, where it activates multiple transcriptional programs that mediate various biological components of the response. While the transcription factor Nfe2l2 is activated by MR, its role in mediating the metabolic effects of dietary MR appears to be non-essential. The hepatic transcriptome responses to MR are largely independent of Nfe2l2, with only minor differences observed in specific metabolic pathways.
Review
Biochemistry & Molecular Biology
Zihang Liu, Panpan Deng, Shengnan Liu, Yiying Bian, Yuanyuan Xu, Qiang Zhang, Huihui Wang, Jingbo Pi
Summary: Cytokine storm refers to a state of the immune system characterized by excessive release of cytokines, leading to inflammation, organ failure, and disease outcomes. NRF2, a transcription factor involved in cellular redox homeostasis, has emerged as a potential therapeutic target in preventing and treating cytokine storms. This review summarizes the causes of cytokine storms and the rationale for targeting NRF2 as a therapeutic intervention.
Article
Plant Sciences
Jie Wu, Ying Song, Zi-Sheng Zhang, Jing-Xian Wang, Xuan Zhang, Jian-Ye Zang, Ming-Yi Bai, Lin-Hui Yu, Cheng-Bin Xiang
Summary: This study reveals the critical role of the GAF domain of AtNLP7 in perceiving nitrate deficiency signals and mediating nitrate-triggered ROS signaling. The GAF domain is involved in the transport and activation of AtNLP7 in response to nitrate deficiency, as well as in the regulation of ROS accumulation.
Article
Endocrinology & Metabolism
Jingwei Jiang, John J. Reho, Sajag Bhattarai, Ioana Cherascu, Adam Hedberg-Buenz, Kacie J. Meyer, Fariba Tayyari, Adam J. Rauckhorst, Deng Fu Guo, Donald A. Morgan, Eric B. Taylor, Michael G. Anderson, Arlene Drack, Kamal Rahmouni
Summary: The study demonstrates that deficiency of BBSome in endothelial cells leads to endothelial dysfunction, increased body weight, abnormal hepatic lipid metabolism, and structural and functional abnormalities in the retina.
MOLECULAR METABOLISM
(2021)
Article
Medicine, Research & Experimental
Allison McCrimmon, Kerin M. Cahill, Claudia Kruger, Margaret E. Mangelli, Emily Bouffard, Timothy Dobroski, Kelly N. Michanczyk, Susan J. Burke, Robert C. Noland, Daria Ilatovskaya, Krisztian Stadler
Summary: The importance of healthy mitochondrial function is crucial in preventing chronic kidney disease and diabetic kidney disease. This study reveals that mitochondrial substrate overload leads to renal injury and sex differences play important roles in diabetic kidney disease. The balance of mitochondrial substrate metabolism is crucial in meeting the energy demand of proximal tubules.
Article
Multidisciplinary Sciences
Urko Del Castillo, Rosalind Norkett, Wen Lu, Anna Serpinskaya, Vladimir Gelfand
Summary: Ataxin-2 plays a crucial role in regulating neuronal cytoskeletal dynamics and organelle trafficking, as evidenced by fruit fly models, where its loss led to defects in nervous system development and survival.
Article
Microbiology
Mary Frances Nakamya, Moses B. Ayoola, Leslie A. Shack, Mirghani Mohamed, Edwin Swiatlo, Bindu Nanduri
Summary: Polyamines such as putrescine, cadaverine, and spermidine play significant roles in cellular processes. Streptococcus pneumoniae, an opportunistic human pathogen, must adapt to different types of stress in the host microenvironment. Deletion of arginine decarboxylase leads to increased susceptibility to oxidative, nitrosative, and acid stress in S. pneumoniae, affecting survival in the host.
Article
Multidisciplinary Sciences
Evgenia Fadzeyeva, Cassandra A. A. Locatelli, Natasha A. Trzaskalski, My-Anh Nguyen, Megan E. Capozzi, Branka Vulesevic, Nadya M. Morrow, Peyman Ghorbani, Antonio A. Hanson, Ilka Lorenzen-Schmidt, Mary-Anne Doyle, Richard Seymour, Elodie M. Varin, Morgan D. Fullerton, Jonathan E. Campbell, Erin E. Mulvihill
Summary: Mice lacking DPP4 have improved islet health, glucoregulation, and reduced obesity with HFD feeding. The improvement can be partly attributed to the loss of DPP4 in non-EC types. Beta cell incretin receptors are necessary for DPP4 inhibitor effects on insulin secretion and glucose tolerance in HFD-fed mice.
Article
Cell Biology
Wayne D. Hawkins, Kelsie A. Leary, Devika Andhare, Hana Popelka, Daniel J. Klionsky, Michael J. Ragusa
Summary: In this study, we show that Atg23 primarily exists as a homodimer and interacts with membranes directly through electrostatic interactions, leading to vesicle tethering. We also demonstrate that mutation of a putative amphipathic helix severely impairs the functionality of Atg23, affecting subcellular localization, vesicle tethering, Atg9 binding, and autophagic efficiency.
Article
Cell Biology
Yuxuan Zhen, Tracy L. McGaha, Fred D. Finkelman, Wen-Hai Shao
Summary: Research indicates that Axl promotes mesangial cell proliferation and phagocytosis of apoptotic cells by activating NF-kappa B and mTORC1, with less impact in other cell types.
JOURNAL OF LEUKOCYTE BIOLOGY
(2022)
Article
Gastroenterology & Hepatology
Shiyan Wang, Shanshan Gao, Yong Zeng, Lin Zhu, Yulin Mo, Chi Chun Wong, Yi Bao, Peiran Su, Jianning Zhai, Lina Wang, Fraser Soares, Xin Xu, Huarong Chen, Kebria Hezaveh, Xinpei Ci, Aobo He, Tracy McGaha, Catherine O'Brien, Robert Rottapel, Wei Kang, Jianfeng Wu, Gang Zheng, Zongwei Cai, Jun Yu, Housheng Hansen He
Summary: The study identified a novel oncogenic epitranscriptome axis of YTHDF1-m(6)A-ARHGEF2 that regulates CRC tumorigenesis and metastasis.
Review
Biotechnology & Applied Microbiology
Stefan J. Marciniak, Joseph E. Chambers, David Ron
Summary: Research on drug-like molecules targeting ER stress and UPR has made progress, but limitations still exist. Understanding these limitations is crucial for the development of these molecules into therapeutic drugs.
NATURE REVIEWS DRUG DISCOVERY
(2022)
Article
Oncology
Alyssa D. Merting, Dakota B. Poschel, Chunwan Lu, John D. Klement, Dafeng Yang, Honglin Li, Huidong Shi, Eric Chapdelaine, Mitzi Montgomery, Michael T. Redman, Natasha M. Savage, Asha Nayak-Kapoor, Kebin Liu
Summary: The study explores the potential of restoring FAS expression in suppressing colorectal tumor growth. Through the administration of nanoparticles carrying FAS cDNA, FAS expression was successfully restored in tumor cells. In vivo and in vitro experiments confirmed that restored FAS expression could eliminate tumor cells and inhibit tumor growth through FASL-induced immune responses.
Article
Hematology
Michael C. Zaiken, Ryan Flynn, Katelyn G. Paz, Stephanie Y. Rhee, Sujeong Jin, Fathima A. Mohamed, Asim Saha, Govindarajan Thangavelu, Paul M. C. Park, Matthew L. Hemming, Peter T. Sage, Arlene H. Sharpe, Michel DuPage, Jeffrey A. Bluestone, Angela Panoskaltsis-Mortari, Corey S. Cutler, John Koreth, Joseph H. Antin, Robert J. Soiffer, Jerome Ritz, Leo Luznik, Ivan Maillard, Geoffrey R. Hill, Kelli P. A. MacDonald, David H. Munn, Jonathan S. Serody, William J. Murphy, Leslie S. Kean, Yi Zhang, James E. Bradner, Jun Qi, Bruce R. Blazar
Summary: In this study, the efficacy of two inhibitors, JQ5 and JQ1, in improving the pathological processes of chronic graft-versus-host-disease (cGVHD) and bronchiolitis obliterans (BO) was tested in a murine model. The results showed that these inhibitors improved pulmonary function, inhibited the germinal center reaction, and reduced the severity of cutaneous lesions. The study suggests that targeting epigenetic processes in the germinal center could be a viable clinical approach for the treatment of cGVHD.
Article
Oncology
Nada S. Aboelella, Caitlin Brandle, Ogacheko Okoko, Md Yeashin Gazi, Zhi-Chun Ding, Hongyan Xu, Gregory Gorman, Roni Bollag, Marco L. Davila, Locke J. Bryan, David H. Munn, Gary A. Piazza, Gang Zhou
Summary: This study demonstrates that the use of indomethacin (indo) can enhance the killing effect of genetically modified T cells on cancer cells by increasing death receptor signaling in cancer cells. This provides a rationale for combining indo with genetically modified T cells to intensify tumor cell killing.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Oncology
Jessica K. Mandula, Shiun Chang, Eslam Mohamed, Rachel Jimenez, Rosa A. Sierra-Mondragon, Darwin C. Chang, Alyssa N. Obermayer, Carlos M. Moran-Segura, Satyajit Das, Julio A. Vazquez-Martinez, Karol Prieto, Ann Chen, Keiran S. M. Smalley, Brian Czerniecki, Peter Forsyth, Richard C. Koya, Brian Ruffell, Juan R. Cubillos- Ruiz, David H. Munn, Timothy I. Shaw, Jose R. Conejo-Garcia, Paulo C. Rodriguez
Summary: The deletion or inhibition of PERK in cancer cells triggers activation of anti-tumor T cell immunity, attenuates tumor growth, and promotes immunogenic cell death. This mechanism provides a potential new target for cancer immunotherapy.
Article
Cell Biology
Luke A. A. Perera, David Ron
Summary: The ER-localized Hsp70 chaperone, BiP, undergoes a rapid and reversible modification called AMPylation, which complements the unfolded protein response in regulating protein folding demand in the ER. This modification is mediated by the enzyme FICD, which also has the ability to deAMPylate BiP. The structural basis of BiP recognition by FICD and the potential physiological significance of BiP AMPylation are also discussed.
COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY
(2023)
Review
Cell Biology
Hannah R. Moorman, Yazmin Reategui, Dakota B. Poschel, Kebin Liu
Summary: IRF8 is a transcription factor that plays an important role in myeloid cell differentiation and immune suppressive cells, and it is often silenced in human cancer patients. It regulates cell apoptosis and the expression of Osteopontin, affecting tumor development and treatment.
Article
Medicine, Research & Experimental
Luke A. Perera, Andrew T. Hattersley, Heather P. Harding, Matthew N. Wakeling, Sarah E. Flanagan, Ibrahim Mohsina, Jamal Raza, Alice Gardham, David Ron, Elisa De Franco
Summary: Mutation in the FICD gene leads to dysfunction of the endoplasmic reticulum, resulting in cell loss and diabetes mellitus. The study suggests that regulating the activity of FICD may provide therapeutic benefits for treating related diseases.
EMBO MOLECULAR MEDICINE
(2023)
Article
Cell Biology
Dakota B. Poschel, Mercy Kehinde-Ige, John D. Klement, Dafeng Yang, Alyssa D. Merting, Natasha M. Savage, Huidong Shi, Kebin Liu
Summary: In this study, it was found that interferon regulatory factor 8 (IRF8) functions as a regulator of tumor cell sensitivity to intrinsic ferroptosis by repressing p53 expression. Restoring IRF8 expression can suppress tumor growth. In human cancer patients, nivolumab responders have higher IRF8 expression in tumor cells compared to non-responders.
Article
Oncology
John D. Klement, Priscilla S. Redd, Chunwan Lu, Alyssa D. Merting, Dakota B. Poschel, Dafeng Yang, Natasha M. Savage, Gang Zhou, David H. Munn, Padraic G. Fallon, Kebin Liu
Summary: This study found that tumor cell surface PD-L1 does not suppress cytotoxic T lymphocyte activity and has no effect on primary tumor growth. However, deletion of tumor cell surface PD-L1 decreases lung metastasis in a CTL-dependent manner. Depletion of myeloid cells or knocking out PD-1 in myeloid cells impairs PD-L1 promotion of tumor lung metastasis. Single-cell RNA sequencing revealed that PD-L1 engages myeloid cells PD-1 to activate SHP2 and repress the IFN-I-STAT1-CXCL9 pathway to impair CTL recruitment in lung metastasis.
Article
Oncology
Gia-Buu Tran, Jane Ding, Bingwei Ye, Mengling Liu, Yajie Yu, Yunhong Zha, Zheng Dong, Kebin Liu, Sunil Sudarshan, Han-Fei Ding
Article
Oncology
Yingcui Yang, Mingqing Zhang, Yongdan Zhang, Kebin Liu, Chunwan Lu
Summary: 5-Fluorouracil (5-FU) selectively kills myeloid-derived suppressor cells (MDSCs) and increases cytotoxic T lymphocyte activation, leading to enhanced antitumor immunity in colorectal cancer patients. The molecular mechanism underlying 5-FU's suppression of MDSCs involves the activation of the p53-Fas pathway, which upregulates Fas expression and increases MDSC sensitivity to apoptosis. 5-FU therapy effectively suppresses MDSC accumulation and promotes CTL tumor infiltration.
Article
Immunology
Govindarajan Thangavelu, Gabriela Andrejeva, Sara Bolivar-Wagers, Sujeong Jin, Michael C. Zaiken, Michael Loschi, Ethan G. Aguilar, Scott N. Furlan, Chrysothemis C. Brown, Yu-Chi Lee, Cameron McDonald Hyman, Colby J. Feser, Angela Panoskaltsis-Mortari, Keli L. Hippen, Kelli P. MacDonald, William J. Murphy, Ivan Maillard, Geoffrey R. Hill, David H. Munn, Robert Zeiser, Leslie S. Kean, Jeffrey C. Rathmell, Hongbo Chi, Randolph J. Noelle, Bruce R. Blazar
Summary: This study investigated how RA receptor signaling in Tregs influences their function and stability in vivo. The results indicate that RA signaling acts as a rheostat to balance Treg function in inflammatory and noninflammatory conditions.
CELLULAR & MOLECULAR IMMUNOLOGY
(2022)