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Mechanisms of Eukaryotic Translation Initiation

Description: PUBLIC HEALTH RELEVANCE: Using structural methods we will study mechanisms of eukaryotic translation initiation. We will investigate routes for inhibiting this process to develop novel anti-tumor agents. We also will study the complex of the scaffold protein eIF4G with the RNA helicase eIF4A and the interaction of factors eIF5, eIF1 and eIF1A, which support start codon recognition by interacting with eIF2.

Funder: National Cancer Institute

Funding type: research

Funder scheme: R01

Start date: 1996-05-08

End date: 2016-01-31

Investigator: GERHARD WAGNER

Institution: HARVARD MEDICAL SCHOOL

Topic: PI3K/AKT/mTOR signaling in cancer

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Funded outputs count: 35

Funder award ID: R01CA068262

OpenAlex ID: G6439694399

Molecular Landscape of the Ribosome Pre-initiation Complex during mRNA Scanning: Structural Role for eIF3c and Its Control by eIF5

2017 · Eiji Obayashi, Rafael E. Luna, et al. · Cell Reports · 65

Identification of DNA primase inhibitors via a combined fragment-based and virtual screening

2016 · Stefan Ilic, Sabine R. Akabayov, et al. · Scientific Reports · 18

An accurately preorganized IRES RNA structure enables eIF4G capture for initiation of viral translation

2016 · Shunsuke Imai, Parimal Kumar, et al. · Nature Structural & Molecular Biology · 65

Overexpression of eIF5 or its protein mimic 5MP perturbs eIF2 function and induces ATF4 translation through delayed re-initiation

2016 · Caitlin Kozel, Brytteny Thompson, et al. · Nucleic Acids Research · 53

The Role of Dynamics and Allostery in the Inhibition of the eIF4E/eIF4G Translation Initiation Factor Complex

2016 · Nicola Salvi, Evangelos Papadopoulos, et al. · Angewandte Chemie International Edition · 18

Molecular mechanism of the dual activity of 4EGI-1: Dissociating eIF4G from eIF4E but stabilizing the binding of unphosphorylated 4E-BP1

2015 · Naotaka Sekiyama, Haribabu Arthanari, et al. · Proceedings of the National Academy of Sciences · 109

Structure of a herpesvirus nuclear egress complex subunit reveals an interaction groove that is essential for viral replication

2015 · Kendra E. Leigh, Mayuri Sharma, et al. · Proceedings of the National Academy of Sciences · 57

eIF1A augments Ago2-mediated Dicer-independent miRNA biogenesis and RNA interference

2015 · Tingfang Yi, Haribabu Arthanari, et al. · Nature Communications · 49

G-quadruplex structures contribute to the neuroprotective effects of angiogenin-induced tRNA fragments

2014 · Pavel Ivanov, Elizabeth O’Day, et al. · Proceedings of the National Academy of Sciences · 345

Human Translation Initiation Factor eIF4G1 Possesses a Low-Affinity ATP Binding Site Facing the ATP-Binding Cleft of eIF4A in the eIF4G/eIF4A Complex

2014 · Sabine R. Akabayov, Barak Akabayov, et al. · Biochemistry · 2

Structure of the eukaryotic translation initiation factor eIF4E in complex with 4EGI-1 reveals an allosteric mechanism for dissociating eIF4G

2014 · Evangelos Papadopoulos, Simon Jenni, et al. · Proceedings of the National Academy of Sciences · 91

4EGI-1 targets breast cancer stem cells by selective inhibition of translation that persists in CSC maintenance, proliferation and metastasis

2014 · Tingfang Yi, Eihab Kabha, et al. · Oncotarget · 33

1H, 13C, and 15N backbone and sidechain chemical shift assignments for the HEAT2 domain of human eIF4GI

2014 · Katherine A. Edmonds, Gerhard Wagner · Biomolecular NMR Assignments

Synthesis of Rigidified eIF4E/eIF4G Inhibitor-1 (4EGI-1) Mimetic and Their in Vitro Characterization as Inhibitors of Protein–Protein Interaction

2014 · Poornachandran Mahalingam, Khuloud Takrouri, et al. · Journal of Medicinal Chemistry · 28

Quantitative phosphoproteomic analysis reveals system-wide signaling pathways downstream of SDF-1/CXCR4 in breast cancer stem cells

2014 · Tingfang Yi, Bo Zhai, et al. · Proceedings of the National Academy of Sciences · 124

3‐Substituted Indazoles as Configurationally Locked 4EGI‐1 Mimetics and Inhibitors of the eIF4E/eIF4G Interaction

2014 · Revital Yefidoff‐Freedman, Ting Chen, et al. · ChemBioChem · 18

Enhanced eIF1 binding to the 40S ribosome impedes conformational rearrangements of the preinitiation complex and elevates initiation accuracy

2013 · Pilar Martin-Marcos, Jagpreet S. Nanda, et al. · RNA · 41

The Interaction between Eukaryotic Initiation Factor 1A and eIF5 Retains eIF1 within Scanning Preinitiation Complexes

2013 · Rafael E. Luna, Haribabu Arthanari, et al. · Biochemistry · 44

Examining weak protein–protein interactions in start codon recognition via NMR spectroscopy

2013 · Rafael E. Luna, Sabine R. Akabayov, et al. · FEBS Journal · 12

β-Hairpin Loop of Eukaryotic Initiation Factor 1 (eIF1) Mediates 40 S Ribosome Binding to Regulate Initiator tRNAMet Recruitment and Accuracy of AUG Selection in Vivo

2013 · Pilar Martin-Marcos, Jagpreet Nanda, et al. · Journal of Biological Chemistry · 47

Molecular Crowding Enhanced ATPase Activity of the RNA Helicase eIF4A Correlates with Compaction of Its Quaternary Structure and Association with eIF4G

2013 · Sabine R. Akabayov, Barak Akabayov, et al. · Journal of the American Chemical Society · 45

Hypoxia-inducible Factor-1α (HIF-1α) Promotes Cap-dependent Translation of Selective mRNAs through Up-regulating Initiation Factor eIF4E1 in Breast Cancer Cells under Hypoxia Conditions

2013 · Tingfang Yi, Evangelos Papadopoulos, et al. · Journal of Biological Chemistry · 62

Backbone resonance assignment of the HEAT1-domain of the human eukaryotic translation initiation factor 4GI

2013 · Sabine R. Akabayov, Gerhard Wagner · Biomolecular NMR Assignments · 5

Tumor suppression by small molecule inhibitors of translation initiation

2012 · Limo Chen, Bertal H Aktas, et al. · Oncotarget · 104

The C-Terminal Domain of Eukaryotic Initiation Factor 5 Promotes Start Codon Recognition by Its Dynamic Interplay with eIF1 and eIF2β

2012 · Rafael E. Luna, Haribabu Arthanari, et al. · Cell Reports · 72