Contributors: Shashi kiran, Ashraf Dar, Samrendra Kumar Singh, Kyung Yong Lee, Anindya Dutta
... The deubiquitinase USP46 is essential for proliferation and tumor growth of HPV-transformed cancers. High-risk Human Papilloma Viruses (HPV) cause cervical, anal and oropharyngeal cancers, unlike the low-risk HPVs, which cause benign lesions. E6 oncoproteins from the high-risk strains are essential for cell proliferation and transformation in HPV induced cancers. We report that a cellular deubiquitinase, USP46 is selectively recruited by the E6 of high-risk, but not low-risk, HPV to deubiqutinate and stabilize Cdt2/DTL. Stabilization of Cdt2, a component of the CRL4Cdt2 E3 ubiquitin ligase, limits the level of Set8, an epigenetic writer, and promotes cell-proliferation. USP46 is essential for the proliferation of HPV-transformed cells, but not of cells without HPV. Cdt2 is elevated in human cervical cancers and knockdown of USP46 inhibits HPV-transformed tumor growth in xenografts. Recruitment of a cellular deubiquitinase to stabilize key cellular proteins is an important activity of oncogenic E6, and the importance of E6-USP46-Cdt2-Set8 pathway in HPV-induced cancers makes USP46 a target for the therapy of such cancers.
Study 'Exon junction complex shapes the transcriptome by repressing recursive splicing' by Blazquez et al
Contributors: Jernej Ule
... The data was produced by Qiaxcel for quantification of splice variants as part of the study 'Exon junction complex shapes the transcriptome by repressing recursive splicing' by Blazquez et al.
Contributors: Volker Boehm, Thiago Britto-Borges, Anna-Lena Steckelberg, Kusum K. Singh, Jennifer V. Gerbracht, Elif Gueney, Lorea Blazquez, Janine Altmüller, Christoph Dieterich, Niels H. Gehring
... This dataset contains the source data for the manuscript titled "Exon junction complexes suppress spurious splice sites to safeguard transcriptome integrity". The unprocessed and uncompressed imaging data for each main and supplemental figure can be found in the respective figure folder. The PDF files "OverviewMainRawImageData" and "OverviewSupplementRawImageData" in the respective folder provide an overview of all main and supplemental figure images used in this study.
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Autoregulation of class II alpha PI3K activity by its lipid binding PX-C2 domain module. Wang et al.
Contributors: Oscar Vadas
... Radiographs of lipid kinase activity assays comparing WT and mutated enzymes.
Contributors: Quan Zhu
... Heterochromatic repetitive satellite RNAs are extensively transcribed in a variety of human cancers, including BRCA1-mutant breast cancer. Aberrant expression of satellite RNAs in cultured cells induces the DNA damage response, activates cell cycle checkpoints, and causes defects in chromosome segregation. However, the mechanism by which satellite RNA expression leads to genomic instability is not well understood. Here, we provide the first evidence that increased levels of satellite RNAs in mammary glands induce tumor formation in mice. Using mass spectrometry, we further show that genomic instability induced by satellite RNAs occurs through interactions with BRCA1-associated protein networks required for the stabilization of DNA replication forks. Additionally formation of RNA-DNA hybrids contributes to DNA replication defects in cells expressing satellite RNAs. These studies lay the foundation for developing novel therapeutic strategies that block the effects of non-coding satellite RNAs in cancer cells.
Contributors: Barry Sleckman, Putzer Hung
... These are the original data files for the Molecular Cell manuscript titled "MRI is a DNA Damage Response Adaptor during Classical Non-Homologous End Joining" by Hung et al. The paper characterizes the role of a small disordered peptide MRI (modulator of retrovirus infection, also known as CYREN) in promoting non-homologous end joining (NHEJ). Specifically, MRI associates with diverse DNA damage response factors at its termini and increases their avidity for chromatin at DNA double-strand breaks (DSBs). Moreover, MRI functions redundantly with XLF in DSB repair, and the loss of both proteins severely impairs V(D)J recombination in lymphocytes and leads to embryonic lethality in mice. We thus purpose that MRI acts as an adaptor that helps to enhance the efficiency of NHEJ.
A systematic p53 mutation library links differential functional impact to cancer mutation pattern and evolutionary conservation. Kotler et al.
Contributors: Eran Kotler
... Microscopy images of growing spheroids in ultra-low adherence plates
Contributors: Argyris Papantonis
... These are raw images of western blots included in Zirkel, A. et al. (2018), Molecular Cell.
Discovery and characterization of ZUFSP, a novel DUB class important for genome stability, Kwasna et al.
Contributors: Ian Gibbs-Seymour
... Original files for the microscopy images in Figures 6 and 7