Molecular Cell

Raw image data relating to the manuscript Dunphy et al., (2018). Non-canonical activation of the DNA sensing adaptor STING by ATM and IFI16 mediates NF-kB activation after nuclear DNA damage.

The mammalian Target Of Rapamycin Complex 1 (mTORC1) signaling system plays a critical role in maintenance of cellular homeostasis by sensing and integrating multiple extracellular and intracellular cues. Therefore, uncovering the effectors of mTORC1 signaling is pivotal to understanding its pathophysiological effects. Here we report that the transcription factor forkhead/winged helix family k1 (Foxk1) is a mediator of mTORC1-regulated gene expression. Surprisingly, Foxk1 phosphorylation is increased upon mTORC1 suppression, which elicits 14-3-3 interaction, a reduction of DNA binding and nuclear exclusion. Mechanistically, this occurs by mTORC1-dependent suppression of nuclear signaling by the Foxk1-kinase, Gsk3. This pathway then regulates the expression of multiple genes associated with glycolysis and downstream anabolic pathways directly modulated by Foxk1 and/or by Foxk1-regulated expression of Hif-1. Thus, Foxk1 mediates mTORC1-driven metabolic rewiring and is likely to be critical for metabolic diseases where improper mTORC1 signaling plays an important role.

The BRCT domains of the BRCA1 and BARD1 tumor suppressors differentially regulate homology-directed repair and stalled fork protection. Billing et al.

Original data of western and EMSA

This dataset contains the raw, unprocessed immunofluorescence, live-cell imaging and Western blot data for the manuscript entitled: Interactome rewiring following pharmacological targeting of BET bromodomains. All methods employed to generate this dataset can be found in the accompanying manuscript and supplemental material.

Adenomatous polyposis coli (APC) and Axin are core components of the beta-catenin destruction complex. How APC’s function is regulated and whether Wnt signaling influences the direct APC-Axin interaction to inhibit the beta-catenin destruction complex and not clear. Through a CRISPR screen of beta-catenin stability, we have identified ICAT, a polypeptide previously known to block beta-catenin-TCF interaction, as a natural inhibitor of APC. ICAT blocks beta-catenin-APC interaction and prevents beta-catenin-mediated APC-Axin interaction, enhancing stabilization of beta-catenin in cells harboring truncated APC or stimulated with Wnt, but not in cells deprived of a Wnt signal. Using ICAT as a tool to disengage beta-catenin-mediated APC-Axin interaction, we demonstrate that Wnt quickly inhibits the direct interaction between APC and Axin. Our study highlights an important scaffolding function of beta-catenin in the assembly of the destruction complex and suggests Wnt-inhibited APC-Axin interaction as a novel mechanism of Wnt-dependent inhibition of the destruction complex.

Original scanned images of western blots/gels and original shift-corrected stack images (IF) of the Figures and Supplemental Figures from the paper "Critical role of the UBL-domain in stimulating the E3 ubiquitin ligase activity of UHRF1 towards chromatin" Foster et al., 2018. Mol Cell.

Fig 3i Gel-shift assay shows the properties of FACT, SSRP1 or SPT16 to promote the deposition of H2A/H2B dimer into tetrasome to form nucleosome. Fig 4a Gel-shift assay shows the DNA binding properties of SSRP1 and SSRP1ΔHMG. Fig 4b Gel-shift assay shows the properties of SSRP1 and SSRP1ΔHMG to promote H2A/H2B dimer deposition onto tetrasome to form nucleosome. Fig S1a EM images of the reconstituted nucleosomes used for the study. Fig S2a SDS-PAGE analysis of the purified FACT and its individual subunits Fig S3a EM images of the reconstituted mono-tetrasomes

Each .ft file represents a different time delay in the ZZ exchange assay, with specific delay information included in the times. txt file. Chemical shift assignments for BMAL1 TAD available at the BMRB.

Data include original unprocessed imaging data relative to Western blots.