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Molecular Cell

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  1. Innate Antiviral Host Defense Attenuates TGF-β Function through IRF3-Mediated Suppression of Smad Signaling

    Molecular Cell 56(6):723 (2014)

    We found that RLR signaling represses TGF-β responses. This regulation is mediated by activated IRF3, using a dual mechanism of IRF3-directed suppression. Activated IRF3 interacts with Smad3, thus inhibiting TGF-β-induced Smad3 activation and, in the nucleus, disrupts functional Smad3 transcription...
  2. Structure of the BRCT repeats of BRCA1 bound to a BACH1 phosphopeptide: implications for signaling.

    Molecular Cell 14(3):405 (2004) PMID 15125843

    We report the crystal structure of the BRCT repeats of human BRCA1 bound to a phosphorylated BACH1 peptide at 2.3 A resolution. The phosphorylated serine 990 and phenylalanine 993 of BACH1 anchor the binding to BRCA1 through specific interactions with a surface cleft at the junction of the two BRCT...
  3. Structural basis for octameric ring formation and DNA interaction of the human homologous-pairing protein Dmc1.

    Molecular Cell 14(3):363 (2004) PMID 15125839

    We crystallized the full-length human Dmc1 protein and solved the structure of the Dmc1 octameric ring. The monomeric structure of the Dmc1 protein closely resembled those of the human and archaeal Rad51 proteins. In addition to the polymerization motif that was previously identified in the Rad51 pr...
  4. Mitotic checkpoint inactivation fosters transformation in cells lacking the breast cancer susceptibility gene, Brca2.

    Molecular Cell 4(1):1 (1999) PMID 10445022

    We report that inactivation of cell cycle checkpoints responsive to mitotic spindle disruption, by mutant forms of p53 or Bub1, relieves growth arrest and initiates neoplastic transformation in primary cells homozygous for truncated Brca2. Tumors from Brca2-deficient animals exhibit dysfunction of t...
  5. SGK3 Mediates INPP4B-Dependent PI3K Signaling in Breast Cancer.

    Molecular Cell 56(4):595 (2014) PMID 25458846 PMCID PMC4255362

    We show that serum and glucocorticoid-regulated kinase 3 (SGK3) is amplified in breast cancer and activated downstream of PIK3CA in a manner dependent on the phosphoinositide phosphatase INPP4B. Expression of INPP4B leads to enhanced SGK3 activation and suppression of Akt phosphorylation. Activation...
  6. Pores of no return.

    Molecular Cell 56(4):465 (2014) PMID 25459877

    In this issue, Bleicken et al. (2014) use double electron-electron resonance (DEER) spectroscopy to propose a new model for the active form of Bax at membranes that differs significantly from those previously proposed. Copyright © 2014 Elsevier Inc. All rights reserved.
  7. Quantitative Proteomics Reveal a Feedforward Mechanism for Mitochondrial PARKIN Translocation and Ubiquitin Chain Synthesis.

    Molecular Cell 56(3):360 (2014) PMID 25284222 PMCID PMC4254048

    We rarely understand quantitatively how ligase activation and ubiquitin (UB) chain assembly are integrated with phosphoregulation. Here we employ quantitative proteomics and live-cell imaging to dissect individual steps in the PINK1 kinase-PARKIN UB ligase mitochondrial control pathway disrupted in...
  8. Lighting Up pre-mRNA recognition.

    Molecular Cell 55(5):649 (2014) PMID 25192362

    Systematic analyses, by UV crosslinking, of the precise binding sites for 23 different proteins across the yeast pre-mRNA population have given insights into the in vivo assembly of, and interactions between, pre-mRNA processing, packaging, and transport complexes. Copyright © 2014 Elsevier Inc. All...
  9. Regulation of active DNA demethylation by an α-crystallin domain protein in Arabidopsis.

    Molecular Cell 55(3):361 (2014) PMID 25002145

    We identified IDM2 (increased DNA methylation 2) as a regulator of DNA demethylation and gene silencing. IDM2 dysfunction causes DNA hypermethylation and silencing of reporter genes and some endogenous genes. These effects of idm2 mutations are similar to those of mutations in IDM1, a regulator of a...
  10. An AMPK-independent signaling pathway downstream of the LKB1 tumor suppressor controls Snail1 and metastatic potential.

    Molecular Cell 55(3):436 (2014) PMID 25042806 PMCID PMC4151130

    We discovered that the epithelial-to-mesenchymal transition transcription factor Snail1 was uniquely upregulated upon LKB1 deficiency across cell types. The ability of LKB1 to suppress Snail1 levels was independent of AMPK but required the related kinases MARK1 and MARK4. In a screen for substrates...