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Cryo-EM of Ribosomal 80S Complexes with Termination Factors Reveals the Translocated Cricket Paralysis Virus IRES.
We present cryoelectron microscopy (cryo-EM) maps of 80S⋅CrPV-STOP⋅eRF1⋅eRF3⋅GMPPNP and 80S⋅CrPV-STOP⋅eRF1 complexes, revealing a previously unseen binding state of the IRES and directly rationalizing that an eEF2-dependent translocation of the IRES is required to allow the first A-site occupation....
Roadblock termination by reb1p restricts cryptic and readthrough transcription.
We describe here an additional mechanism of transcription termination for RNAPII and demonstrate its biological significance. We show that the transcriptional activator Reb1p bound to DNA is a roadblock for RNAPII, which pauses and is ubiquitinated, thus triggering termination. Reb1p-dependent termi...
The two faces of receptor interacting protein kinase-1.
Receptor Interacting Protein Kinase-1 (RIPK1), a key player in inflammation and cell death, assumes opposite functions depending on the cellular context and its posttranslational modifications. Genetic evidence supported by biochemical and cellular biology approaches sheds light on the circumstances...
Selective Protein Denitrosylation Activity of Thioredoxin-h5 Modulates Plant Immunity
We show that in plant immunity the oxidoreductase Thioredoxin-h5 (TRXh5) reverses SNO modifications by acting as a selective protein-SNO reductase. While TRXh5 failed to restore immunity in gsnor1 mutants that display excessive accumulation of the NO donor S-nitrosoglutathione, it rescued immunity i...
Suv39h-dependent H3K9me3 marks intact retrotransposons and silences LINE elements in mouse embryonic stem cells.
We dissected Suv39h-dependent histone H3 lysine 9 trimethylation (H3K9me3) by genome-wide ChIP sequencing in mouse embryonic stem cells (ESCs). Refined bioinformatic analyses of repeat subfamilies indicated selective accumulation of Suv39h-dependent H3K9me3 at interspersed repetitive elements that c...
PCNA and Msh2-Msh6 activate an Mlh1-Pms1 endonuclease pathway required for Exo1-independent mismatch repair.
We identified 14 mutations in POL30, which encodes PCNA in Saccharomyces cerevisiae, specific to Exo1-independent MMR. The mutations identified affected amino acids at three distinct sites on the PCNA structure. Multiple mutant PCNA proteins had defects either in trimerization and Msh2-Msh6 binding...
Visualization of transient protein-protein interactions that promote or inhibit amyloid assembly.
We identify the interactions that inhibit or promote fibril formation in atomic detail. The results reveal that different outcomes of assembly result from biomolecular interactions involving similar surfaces. Specifically, inhibition occurs via rigid body docking of monomers in a head-to-head orient...
Akt phosphorylation and regulation of transketolase is a nodal point for amino acid control of purine synthesis.
We showed previously that depriving cells of a single essential amino acid rapidly and reversibly arrests purine synthesis. Here we demonstrate that amino acids via mammalian target of rapamycin 2 and IκB kinase regulate Akt activity and Akt association and phosphorylation of transketolase (TKT), a...
Gain-of-function mutant p53 promotes cell growth and cancer cell metabolism via inhibition of AMPK activation.
We show here that GOF mutp53s inhibit AMP-activated protein kinase (AMPK) signaling in head and neck cancer cells. Conversely, downregulation of GOF mutp53s enhances AMPK activation under energy stress, decreasing the activity of the anabolic factors acetyl-CoA carboxylase and ribosomal protein S6 a...
Regulating microtubules and genome stability via the CUL7/3M syndrome complex and CUL9.
In this issue, two studies from Yue Xiong and colleagues (Li et al., 2014; Yan et al., 2014) show that CUL7, OBSL1, and CCDC8, all mutated in 3M short stature syndrome, form a centrosomal complex that regulates CUL9 and its substrate survivin to link mitosis to cell survival. Copyright © 2014 Elsevi...