Article
Multidisciplinary Sciences
Tasniem Fetian, Brendan M. McShane, Nicole L. Horan, Donya N. Shodja, Jason D. True, Amber L. Mosley, Karen M. Arndt
Summary: Histone modifications coupled to transcription elongation play important roles in regulating gene expression. The Paf1 transcription elongation complex (Paf1C) interacts with the ubiquitin conjugase Rad6 through its histone modification domain (HMD), leading to H2BK123 ubiquitylation. The specific interface between a transcription elongation factor and a ubiquitin conjugase guides substrate selection during active gene expression.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Multidisciplinary Sciences
Min Qiu, Zhinang Yin, Honghong Wang, Lingyu Lei, Conghui Li, Yali Cui, Rong Dai, Peiyuan Yang, Ying Xiang, Qiuzi Li, Junhui Lv, Zhuang Hu, Min Chen, Hai-Bing Zhou, Pingping Fang, Ruijing Xiao, Kaiwei Liang
Summary: The study reveals that Cyclin-dependent kinase 12 (CDK12) interacts with cyclin K to promote transcription elongation. Using chemical genetic and phosphoproteomic screening, a landscape of CDK12 substrates including regulators of transcription, chromatin organization, and RNA splicing was identified. LEO1, a subunit of the polymerase-associated factor 1 complex (PAF1C), was validated as a cellular substrate of CDK12, and its phosphorylation was found to be regulated by the Integrator-PP2A complex (INTAC).
Article
Genetics & Heredity
Adiel Cohen, Emese Pataki, Martin Kupiec, Ronit Weisman
Summary: This study reveals that TORC2 plays a dual role in transcription regulation, negatively regulating gene silencing and positively regulating gene induction in response to stress. The inhibition of Gcn5 accumulation at chromatin by TORC2-Gad8 contributes to gene regulation. Additionally, the loss of SAGA complex and Bdf2 protein can restore gene silencing and transcriptional induction in TORC2 mutant cells and alleviate stress sensitivity.
Article
Multidisciplinary Sciences
Jason J. Kwon, Behnoush Hajian, Yuemin Bian, Lucy C. Young, Alvaro J. Amor, James R. Fuller, Cara V. Fraley, Abbey M. Sykes, Jonathan So, Joshua Pan, Laura Baker, Sun Joo Lee, Douglas B. Wheeler, David L. Mayhew, Nicole S. Persky, Xiaoping Yang, David E. Root, Anthony M. Barsotti, Andrew W. Stamford, Charles K. Perry, Alex Burgin, Frank McCormick, Christopher T. Lemke, William C. Hahn, Andrew J. Aguirre
Summary: This study uses cryo-electron microscopy to determine the structure of the SHOC2-MRAS-PP1C complex and investigate the functional consequences of SHOC2 missense variants. The research reveals the mechanism of complex formation and the enhanced activity of mutant versions. This study is of great importance for understanding cellular signal transduction and the pathogenesis of RAS-related diseases.
Article
Multidisciplinary Sciences
Dina Husein, Ahmed Alamoudi, Yoshio Ohyama, Hanna Mochida, Brigitte Ritter, Yoshiyuki Mochida
Summary: This study investigated the expression and subcellular localization of the WDR72 gene in mouse tissues and cell lines. The researchers found that WDR72 protein was present in both the membranous and cytosolic fractions of ameloblast cell lines, with a predominant localization at the Golgi apparatus. Mutant forms of WDR72 showed different subcellular localization, with a form lacking the C-terminal region being exclusively detected in the cytoplasm. These findings provide new insights into the role of WDR72 in vesicular Golgi transport and its potential relevance to Amelogenesis Imperfecta.
SCIENTIFIC REPORTS
(2022)
Article
Multidisciplinary Sciences
Xueqiang Wang, Xing Zhang, Ke Cao, Mengqi Zeng, Xuyang Fu, Adi Zheng, Feng Zhang, Feng Gao, Xuan Zou, Hao Li, Min Li, Weiqiang Lv, Jie Xu, Jiangang Long, Weijin Zang, Jinghai Chen, Jian Ding, Jiankang Liu, Zhihui Feng
Summary: This study reveals the importance of succinate dehydrogenase complex II assembly in the development of dilated cardiomyopathy and provides insights into potential therapeutic interventions for heart diseases.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Sijia Bao, Chao Xu
Summary: SETD1A and SETD1B, originating from yeast Set1, the sole H3K4 methyltransferase, have important roles in active gene transcription. Our crystal structures of the RRM domains of human SETD1A and SETD1B reveal their structural differences from the yeast homolog. We found that an intrinsically disordered region in SETD1A/B binds WDR82, and the positively charged regions within human RRM domains might be involved in RNA binding. Our work provides structural insight into the assembly of WDR82 with the catalytic subunits SETD1A/B in the context of the whole complex.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Yuki Horisawa-Takada, Chisato Kodera, Kazumasa Takemoto, Akihiko Sakashita, Kenichi Horisawa, Ryo Maeda, Ryuki Shimada, Shingo Usuki, Sayoko Fujimura, Naoki Tani, Kumi Matsuura, Tomohiko Akiyama, Atsushi Suzuki, Hitoshi Niwa, Makoto Tachibana, Takashi Ohba, Hidetaka Katabuchi, Satoshi H. Namekawa, Kimi Araki, Kei-Ichiro Ishiguro
Summary: The study identified a protein complex composed of ZFP541 and KCTD19 as key transcriptional regulators in mouse meiotic prophase progression. This complex promotes the completion of meiotic prophase and triggers the reconstruction of transcriptional network and chromatin organization. ZFP541 binds to and suppresses genes associated with transcriptional regulation and covalent chromatin modification to ensure proper meiotic progression.
NATURE COMMUNICATIONS
(2021)
Article
Cell Biology
Banafsheh Golchoubian, Andreas Brunner, Helena Bragulat-Teixidor, Annett Neuner, Busra A. Akarlar, Nurhan Ozlu, Anne-Lore Schlaitz
Summary: Nuclear pore complexes (NPCs) are channels within the nuclear envelope that mediate nucleocytoplasmic transport, forming through a coordination of protein complex assembly and membrane deformation. REEP4 plays an important role in NPC formation during mitosis, being recruited by the NPC biogenesis factor ELYS. Their cooperation may provide high-curvature ER membrane to the nascent NPC.
JOURNAL OF CELL BIOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Ki-Young Lee, Masahiro Enomoto, Teklab Gebregiworgis, Genevieve M. C. Gasmi-Seabrook, Mitsuhiko Ikura, Christopher B. Marshall
Summary: The study found that KRAS forms dimers and multimers (nanoclusters) on the plasma membrane to drive cell signaling and proliferation. The G12D mutation enhances nanoclustering of KRAS. Through investigating the structure of KRAS on the membrane, it was revealed that the G12D mutant self-associates through an asymmetric 'alpha-beta' interface.
Article
Neurosciences
Atsushi Shimohata, Dilip Rai, Takumi Akagi, Sumiko Usui, Ikuo Ogiwara, Makoto Kaneda
Summary: In this study, the subcellular localization of mGluR6 CTD mutants in 293T cells was investigated using immunocytochemistry, immunoprecipitation, and flow cytometry. The results showed that mGluR6 mutants with 15- and 20-amino acid deletions from the C terminus localized to the ER and were deficient at the cell surface. Introducing an alanine substitution at basic residues within the CTD rescued the surface deficiency of mGluR6 mutants.
MOLECULAR AND CELLULAR NEUROSCIENCE
(2023)
Article
Cell Biology
Cheng-Yao Chiang, Songqing Fan, Hongmei Zheng, Wenjun Guo, Zehan Zheng, Yihua Sun, Chuanqi Zhong, Juan Zeng, Shuaihu Li, Min Zhang, Tian Xiao, Duo Zheng
Summary: This study reveals the tumor-suppressive role of SETD7 in non-small cell lung cancer (NSCLC) by modulating KRAS methylation and degradation. SETD7 interacts with KRAS and methylates KRAS at lysines 182 and 184, leading to KRAS degradation and attenuation of the RAS/MEK/ERK signaling cascade.
Article
Developmental Biology
Mingjie Xu, Jie Yao, Yingchao Shi, Huijuan Yi, Wukui Zhao, Xinhua Lin, Zhongzhou Yang
Summary: The study identified a crucial role of the SRCAP chromatin remodeling complex in mitochondrial maturation and oxidative metabolism during heart development in mice. The complex functions through H2A.Z deposition to activate transcription of metabolic genes, shedding new light on the transcriptional regulation of ubiquinone biosynthesis.
Article
Multidisciplinary Sciences
Albert Serra-Cardona, Shoufu Duan, Chuanhe Yu, Zhiguo Zhang
Summary: The study demonstrates that mutations in replicative helicase subunit, Mcm2, and leading strand DNA polymerase subunit, Dpb3, lead to asymmetric distribution of H3K4me3 during DNA replication, and the H3K4 methyltransferase complex, COMPASS, plays a role in restoring a more symmetric distribution of H3K4me3 at replicating DNA strands during cell cycle progression.
Article
Immunology
Ana C. F. Ferreira, Aydan C. H. Szeto, Paula A. Clark, Alastair Crisp, Patrycja Kozik, Helen E. Jolin, Andrew N. J. McKenzie
Summary: The study found that ADNP plays an indispensable role in immune reactions to allergens by recruiting proteins such as CHD4 and BRG1, serving as a critical bridge in gene activation and promoting T cell differentiation. The absence of ADNP impairs the ability of GATA3 and AP-1 to initiate histone acetylation and DNA accessibility, resulting in impaired expression of type 2 cytokines. These results demonstrate the importance of ADNP in promoting immune cell specialization.
Article
Chemistry, Medicinal
Karolina Mikulska-Ruminska, Indira Shrivastava, James Krieger, She Zhang, Hongchun Li, Hulya Bayir, Sally E. Wenzel, Andrew P. VanDemark, Valerian E. Kagan, Ivet Bahar
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2019)
Article
Genetics & Heredity
Cory M. Nadel, Timothy D. Mackie, Richard G. Gardner
Article
Cell Biology
Aaron J. Plys, Christopher P. Davis, Jongmin Kim, Gizem Rizki, Madeline M. Keenen, Sharon K. Marr, Robert E. Kingston
GENES & DEVELOPMENT
(2019)
Article
Cell Biology
Ramon D. Jones, Charisma Enam, Rebeca Ibarra, Heather R. Borror, Kaitlyn E. Mostoller, Eric K. Fredrickson, JiaBei Lin, Edward Chuang, Zachary March, James Shorter, Tommer Ravid, Gary Kleiger, Richard G. Gardner
MOLECULAR BIOLOGY OF THE CELL
(2020)
Article
Biochemistry & Molecular Biology
Matthew R. Googins, Aigbirhemwen O. Woghiren-Afegbua, Michael Calderon, Claudette M. St Croix, Kirill I. Kiselyov, Andrew P. VanDemark
Article
Neurosciences
Hume Stroud, Marty G. Yang, Yael N. Tsitohay, Christopher P. Davis, Maxwell A. Sherman, Sinisa Hrvatin, Emi Ling, Michael E. Greenberg
Article
Multidisciplinary Sciences
Jinming Zhao, Haider H. Dar, Yanhan Deng, Claudette M. St Croix, Zhipeng Li, Yoshinori Minami, Indira H. Shrivastava, Yulia Y. Tyurina, Emily Etling, Joel C. Rosenbaum, Tadao Nagasaki, John B. Trudeau, Simon C. Watkins, Ivet Bahar, Hulya Bayir, Andy P. VanDemark, Valerian E. Kagan, Sally E. Wenzel
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2020)
Article
Biochemistry & Molecular Biology
Tamil S. Anthonymuthu, Yulia Y. Tyurina, Wan-Yang Sun, Karolina Mikulska-Ruminska, Indira H. Shrivastava, Vladimir A. Tyurin, Fatma B. Cinemre, Haider H. Dar, Andrew P. VanDemark, Theodore R. Holman, Yoel Sadovsky, Brent R. Stockwell, Rong-Rong He, Ivet Bahar, Hulya Bayir, Valerian E. Kagan
Summary: HpETE-PE is a cell death signal in ferroptosis, produced by the 15LOX/PEBP1 complex. Fer-1 does not directly affect 15LOX, but can effectively inhibit the production of HpETE-PE by the 15LOX/PEBP1 complex. This study resolves the long-standing Fer-1 anti-ferroptotic paradox.
Article
Cell Biology
Amanda Bradley, Nicole M. Marsh, Heather R. Borror, Kaitlyn E. Mostoller, Amber Gama, Richard G. Gardner
Summary: Acute ethanol exposure induces sumoylation of specific chromatin structural proteins, dependent on the activity of the E3 SUMO ligase Mms21, in yeast cells. Ethanol exposure also results in the formation of Rad52 foci but does not induce Rad53 phosphorylation.
MOLECULAR BIOLOGY OF THE CELL
(2021)
Article
Biochemistry & Molecular Biology
Rebeca Ibarra, Heather R. Borror, Bryce Hart, Richard G. Gardner, Gary Kleiger
Summary: The yeast PQC ubiquitin ligase San1 contains multiple substrate binding sites along its polypeptide chain, showing specificity for unique misfolded proteins and enabling the formation of high affinity ubiquitin ligase-substrate complexes.
Article
Cell Biology
Andrew P. VanDemark, Stacy L. Hrizo, Samantha L. Eicher, Jules Kowalski, Tracey D. Myers, Megan R. Pfeifer, Kacie N. Riley, Dwight D. Koeberl, Michael J. Palladino
Summary: Triosephosphate isomerase (TPI) deficiency (TPI Df) is an untreatable enzymopathy that leads to anemia, muscular impairment, and brain damage. In this study, a new mutation TPIQ181P and the common mutation TPIE105D were identified in compound heterozygous patients. Surprisingly, these patients did not exhibit neuropathy or cognitive impairment. Biochemical and structural studies revealed that the TPIQ181P mutation resulted in impaired catalytic properties and disorder in the catalytic lid. Genetic complementation between the two alleles was proposed as the mechanism of disease severity.
DISEASE MODELS & MECHANISMS
(2022)
Article
Biochemistry & Molecular Biology
Andrew M. Lamade, Limin Wu, Haider H. Dar, Heather L. Mentrup, Indira H. Shrivastava, Michael W. Epperly, Claudette M. St Croix, Yulia Y. Tyurina, Tamil S. Anthonymuthu, Qin Yang, Aleksandr A. Kapralov, Zhentai Huang, Gaowei Mao, Andrew A. Amoscato, Zachary E. Hier, Margarita A. Artyukhova, Galina Shurin, Joel C. Rosenbaum, Peter J. Gough, John Bertin, Andrew P. VanDemark, Simon C. Watkins, Kevin P. Mollen, Ivet Bahar, Joel S. Greenberger, Valerian E. Kagan, Michael J. Whalen, Hulya Bayir
Summary: Ferroptosis and necroptosis are two pro-inflammatory cell death programs that have gained attention for their potential in treating various diseases. This study shows that inhibiting ferroptosis can improve outcomes after irradiation and brain trauma, and the protein PEBP1 plays a crucial role in regulating the switch between necroptosis and ferroptosis.
Article
Biochemistry & Molecular Biology
S. Branden Van Oss, Saurin Bipin Parikh, Nelson Castilho Coelho, Aaron Wacholder, Ivan Belashov, Sara Zdancewicz, Manuel Michaca, Jiazhen Xu, Yun Pyo Kang, Nathan P. Ward, Sang Jun Yoon, Katherine M. McCourt, Jake McKee, Trey Ideker, Andrew P. VanDemark, Gina M. DeNicola, Anne-Ruxandra Carvunis
Summary: Organisms must synthesize or assimilate essential organic compounds to survive. Met15 has long been considered an essential gene for inorganic sulfur assimilation in yeast. However, our study reveals that the gene YLL058W can also enable cells to assimilate enough inorganic sulfur for survival. This finding has implications for sulfur metabolism research and other related fields.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Haider H. Dar, Karolina Mikulska- Ruminska, Yulia Y. Tyurina, Diane K. Luci, Adam Yasgar, Svetlana N. Samovich, Alexander A. Kapralov, Austin B. Souryavong, Vladimir A. Tyurin, Andrew A. Amoscato, Michael W. Epperly, Galina V. Shurin, Melissa Standley, Theodore R. Holman, Claudette M. St. Croix, Simon C. Watkins, Andrew P. VanDemark, Sandeep Rana, Alexey V. Zakharov, Anton Simeonov, Juan Marugan, Rama K. Mallampalli, Sally E. Wenzel, Joel S. Greenberger, Ganesha Rai, Huelya Bayir, Ivet Bahar, Valerian E. Kagan
Summary: Programmed ferroptotic death eliminates cells in all major organs and tissues through iron-catalyzed lipid peroxidation under inadequate control by thiols. Ferroptosis is associated with the development of chronic degenerative diseases and acute injuries in various organs, making it a potential target for therapeutic intervention. The study focuses on inhibiting the catalytic complex of 15-lipoxygenase (15LOX) and phosphatidylethanolamine (PE)-binding protein 1 (PEBP1), rather than 15LOX alone, as a strategy to discover antiferroptotic agents. The design and testing of a customized library of compounds led to the identification of two lead compounds, FerroLOXIN-1 and 2, which effectively suppress ferroptosis in vitro and in vivo by interacting with the 15LOX-2/PEBP1 complex.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Multidisciplinary Sciences
Kevin G. Hicks, Ahmad A. Cluntun, Heidi L. Schubert, Sean R. Hackett, Jordan A. Berg, Paul G. Leonard, Mariana A. Ajalla Aleixo, Youjia Zhou, Alex J. Bott, Sonia R. Salvatore, Fei Chang, Aubrie Blevins, Paige Barta, Samantha Tilley, Aaron Leifer, Andrea Guzman, Ajak Arok, Sarah Fogarty, Jacob M. Winter, Hee-Chul Ahn, Karen N. Allen, Samuel Block, Iara A. Cardoso, Jianping Ding, Ingrid Dreveny, William C. Gasper, Quinn Ho, Atsushi Matsuura, Michael J. Palladino, Sabin Prajapati, Pengkai Sun, Kai Tittmann, Dean R. Tolan, Judith Unterlass, Andrew P. VanDemark, Matthew G. Vander Heiden, Bradley A. Webb, Cai-Hong Yun, Pengkai Zhao, Bei Wang, Francisco J. Schopter, Christopher P. Hill, Maria Cristina Nonato, Florian L. Muller, James E. Cox, Jared Rutter
Summary: Metabolic networks play a crucial role in various cellular processes. Discovering low-affinity protein-metabolite interactions that govern these networks is challenging. A new method, called mass spectrometry integrated with equilibrium dialysis for the discovery of allostery systematically (MIDAS), was developed to identify such interactions. In a study involving enzymes from human carbohydrate metabolism, 830 protein-metabolite interactions were discovered, including both known and unknown interactions. Some of these interactions were functionally validated, revealing the isoform-specific inhibition of lactate dehydrogenase by long-chain acyl-coenzyme A. The findings suggest that these protein-metabolite interactions contribute to the adaptive metabolic flexibility in different tissues.