The STUbL RNF4 regulates protein group SUMOylation by targeting the SUMO conjugation machinery

Cancer Signaling networks and Molecular Therapeutic

3D modeling and motion parallax for improved videoconferencing

We consider a face-to-face videoconferencing system that uses a Kinect camera at each end of the link for 3D modeling and an ordinary 2D display for output. The Kinect camera allows a 3D model of each participant to be transmitted; the (assumed static) background is sent separately. Furthermore, the Kinect tracks the receiver’s head, allowing our system to render a view of the sender depending on the receiver’s viewpoint. The resulting motion parallax gives the receivers a strong impression of 3D viewing as they move, yet the system only needs an ordinary 2D display. This is cheaper than a full 3D system, and avoids disadvantages such as the need to wear shutter glasses, VR headsets, or to sit in a particular position required by an autostereo display. Perceptual studies show that users experience a greater sensation of depth with our system compared to a typical 2D videoconferencing system

Personalization for unobtrusive service interaction

Increasingly, mobile devices play a key role in the communication between users and the services embedded in their environment. With ever greater number of services added to our surroundings, there is a need to personalize services according to the user needs and environmental context avoiding service behavior from becoming overwhelming. In order to prevent this information overload, we present a method for the development of mobile services that can be personalized in terms of obtrusiveness (the degree in which each service intrudes the user's mind) according to the user needs and preferences. That is, services can be developed to provide their functionality at different obtrusiveness levels depending on the user by minimizing the duplication of efforts. On the one hand, we provide mechanisms for describing the obtrusiveness degree required for a service. On the other hand, we make use of Feature Modeling techniques in order to define the obtrusiveness level adaptation in a declarative manner. An experiment was conducted in order to put in practice the proposal and evaluate the user acceptance for the personalization capabilities provided by our approach. © Springer-Verlag London Limited 2011.This work has been developed with the support of MICINN under the project EVERYWARE TIN2010-18011 and co-financed with ERDF, in the grants program FPU.Gil Pascual, M.; Giner Blasco, P.; Pelechano Ferragud, V. (2012). Personalization for unobtrusive service interaction. Personal and Ubiquitous Computing. 16(5):543-561. https://doi.org/10.1007/s00779-011-0414-0S543561165Abrams M, Phanouriou C, Batongbacal AL, Williams SM, Shuster JE (1999) Uiml: an appliance-independent xml user interface language. In: WWW ’99. Elsevier, North-Holland, pp 1695–1708Ballagas R, Borchers J, Rohs M, Sheridan JG (2006) The smart phone: a ubiquitous input device. 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New Riders Press, USACalvary G, Coutaz J, Thevenin D, Limbourg Q, Bouillon L, Vanderdonckt J (2003) A unifying reference framework for multi-target user interfaces. Interact Comput 15(3):289–308Cetina C, Giner P, Fons J, Pelechano V (2009) Autonomic computing through reuse of variability models at runtime: the case of smart homes. Computer 42(10):37–43Chatfield C, Carmichael D, Hexel R, Kay J, Kummerfeld B (2005) Personalisation in intelligent environments: managing the information flow. In: OZCHI ’05. Computer-human interaction special interest group of Australia, pp 1–10Clerckx T, Winters F, Coninx K (2005) Tool support for designing context-sensitive user interfaces using a model-based approach. In: TAMODIA ’05: Proceedings of the 4th international workshop on Task models and diagrams. ACM Press, New York, pp 11–18Czarnecki K, Helsen S, Eisenecker U (2004) Staged configuration using feature models. In: Proceedings of SPLCDuarte C, Carriço L (2006) A conceptual framework for developing adaptive multimodal applications. In: Proceedings of IUI ’06. ACM, New York, pp 132–139Evans (2003) Domain-driven design: tacking complexity In the heart of software. Addison-Wesley Longman Publishing Co., Inc., BostonsFavre JM (2004) Foundations of model (Driven) (Reverse) engineering: models—Episode I: stories of the fidus papyrus and of the solarus. In: Bezivin J, Heckel R (eds) Language engineering for model-driven software development, no. 04101, Dagstuhl seminar proceedings. Dagstuhl, GermanyFischer G (2001) User modeling in human–computer interaction. User Model User-Adap Inter 11(1–2):65–86Gibbs WW (2005) Considerate computing. Scientific American 292(1):54–61Giner P, Cetina C, Fons J, Pelechano V (2010) Developing mobile workflow support in the internet of things. IEEE Pervas Comput 9(2):18–26Giner P, Cetina C, Fons J, Pelechano V (2011) Implicit interaction design for pervasive workflows. Pers Ubiquit Comput 1–10Gulliksen J, Goransson B, Boivie I, Blomkvist S, Persson J, Cajander A (2003) Key principles for user-centred systems design. Behav Inform Technol 22:397–409Hinckley K, Horvitz E (2001) Toward more sensitive mobile phones. In: Proceedings of the UIST ’01. ACM, New York, pp 191–192Ho J, Intille SS (2005) Using context-aware computing to reduce the perceived burden of interruptions from mobile devices. In: Proceedings of CHI ’05. ACM, New York, pp 909–918Horvitz E, Kadie C, Paek T, Hovel D (2003) Models of attention in computing and communication: from principles to applications. Commun ACM 46(3):52–59Ju W, Leifer L (2008) The design of implicit interactions: making interactive systems less obnoxious. Des Issues 24(3):72–84Lewis JR (1995) Ibm computer usability satisfaction questionnaires: psychometric evaluation and instructions for use. 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Splicing factors control triple-negative breast cancer cell mitosis through SUN2 interaction and sororin intron retention

BackgroundTriple negative breast cancer (TNBC) is an aggressive subtype of breast cancer with limited therapeutic opportunities. Recently, splicing factors have gained attention as potential targets for cancer treatment. Here we systematically evaluated the role of RNA splicing factors in TNBC cell proliferation.MethodsIn this study, we performed an RNAi screen targeting 244 individual splicing factors to systematically evaluate their role in TNBC cell proliferation. For top candidates, mechanistic insight was gained using amongst others western blot, PCR, FACS, molecular imaging and cloning. Pulldown followed by mass spectrometry were used to determine protein-protein interactions and patient-derived RNA sequencing data was used relate splicing factor expression levels to proliferation markers.ResultsWe identified nine splicing factors, including SNRPD2, SNRPD3 and NHP2L1, of which depletion inhibited proliferation in two TNBC cell lines by deregulation of sister chromatid cohesion (SCC) via increased sororin intron 1 retention and down-regulation of SMC1, MAU2 and ESPL1. Protein-protein interaction analysis of SNRPD2, SNRPD3 and NHP2L1 identified that seven out of the nine identified splicing factors belong to the same spliceosome complex including novel component SUN2 that was also critical for efficient sororin splicing. Finally, sororin transcript levels are highly correlated to various proliferation markers in BC patients.ConclusionWe systematically determined splicing factors that control proliferation of breast cancer cells through a mechanism that involves effective sororin splicing and thereby appropriate sister chromatid cohesion. Moreover, we identified SUN2 as an important new spliceosome complex interacting protein that is critical in this process. We anticipate that deregulating sororin levels through targeting of the relevant splicing factors might be a potential strategy to treat TNBC.Cancer Signaling networks and Molecular Therapeutic

Global non-covalent SUMO interaction networks reveal SUMO-dependent stabilization of the non-homologous end joining complex

In contrast to our extensive knowledge on covalent small ubiquitin-like modifier (SUMO) target proteins, we are limited in our understanding of non-covalent SUMO-binding proteins. We identify interactors of different SUMO isoforms-monomeric SUMO1, monomeric SUMO2, or linear trimeric SUMO2 chains-using a mass spectrometry-based proteomics approach. We identify 379 proteins that bind to different SUMO isoforms, mainly in a preferential manner. Interestingly, XRCC4 is the only DNA repair protein in our screen with a preference for SUMO2 trimers over mono-SUMO2, as well as the only protein in our screen that belongs to the non-homologous end joining (NHEJ) DNA double-strand break repair pathway. A SUMO interaction motif (SIM) in XRCC4 regulates its recruitment to sites of DNA damage and phosphorylation of S320 by DNA-PKcs. Our data highlight the importance of non-covalent and covalent sumoylation for DNA double-strand break repair via the NHEJ pathway and provide a resource of SUMO isoform interactors.Cancer Signaling networks and Molecular Therapeutic

Total Chemical Synthesis of SUMO and SUMO-Based Probes for Profiling the Activity of SUMO-Specific Proteases

Chemical Immunolog

A proteomics study identifying interactors of the FSHD2 gene product SMCHD1 reveals RUVBL1-dependent DUX4 repression

Structural Maintenance of Chromosomes Hinge Domain Containing 1 (SMCHD1) is a chromatin repressor, which is mutated in > 95% of Facioscapulohumeral dystrophy (FSHD) type 2 cases. In FSHD2, SMCHD1 mutations ultimately result in the presence of the cleavage stage transcription factor DUX4 in muscle cells due to a failure in epigenetic repression of the D4Z4 macrosatellite repeat on chromosome 4q, which contains the DUX4 locus. While binding of SMCHD1 to D4Z4 and its necessity to maintain a repressive D4Z4 chromatin structure in somatic cells are well documented, it is unclear how SMCHD1 is recruited to D4Z4, and how it exerts its repressive properties on chromatin. Here, we employ a quantitative proteomics approach to identify and characterize novel SMCHD1 interacting proteins, and assess their functionality in D4Z4 repression. We identify 28 robust SMCHD1 nuclear interactors, of which 12 are present in D4Z4 chromatin of myocytes. We demonstrate that loss of one of these SMCHD1 interacting proteins, RuvB-like 1 (RUVBL1), further derepresses DUX4 in FSHD myocytes. We also confirm the interaction of SMCHD1 with EZH inhibitory protein (EZHIP), a protein which prevents global H3K27me3 deposition by the Polycomb repressive complex PRC2, providing novel insights into the potential function of SMCHD1 in the repression of DUX4 in the early stages of embryogenesis. The SMCHD1 interactome outlined herein can thus provide further direction into research on the potential function of SMCHD1 at genomic loci where SMCHD1 is known to act, such as D4Z4 repeats, the inactive X chromosome, autosomal gene clusters, imprinted loci and telomeres.Cancer Signaling networks and Molecular Therapeutic

Zinc finger protein ZNF384 is an adaptor of Ku to DNA during classical non-homologous end-joining

Classical non-homologous end-joining (cNHEJ) is the dominant pathway used by human cells to repair DNA double-strand breaks (DSBs) and maintain genome stability. Here the authors show that PARP1-driven chromatin expansion allows the recruitment of ZNF384, which in turn recruits Ku70/Ku80 to facilitate cNHEJ.DNA double-strand breaks (DSBs) are among the most deleterious types of DNA damage as they can lead to mutations and chromosomal rearrangements, which underlie cancer development. Classical non-homologous end-joining (cNHEJ) is the dominant pathway for DSB repair in human cells, involving the DNA-binding proteins XRCC6 (Ku70) and XRCC5 (Ku80). Other DNA-binding proteins such as Zinc Finger (ZnF) domain-containing proteins have also been implicated in DNA repair, but their role in cNHEJ remained elusive. Here we show that ZNF384, a member of the C2H2 family of ZnF proteins, binds DNA ends in vitro and is recruited to DSBs in vivo. ZNF384 recruitment requires the poly(ADP-ribosyl) polymerase 1 (PARP1)-dependent expansion of damaged chromatin, followed by binding of its C2H2 motifs to the exposed DNA. Moreover, ZNF384 interacts with Ku70/Ku80 via its N-terminus, thereby promoting Ku70/Ku80 assembly and the accrual of downstream cNHEJ factors, including APLF and XRCC4/LIG4, for efficient repair at DSBs. Altogether, our data suggest that ZNF384 acts as a 'Ku-adaptor' that binds damaged DNA and Ku70/Ku80 to facilitate the build-up of a cNHEJ repairosome, highlighting a role for ZNF384 in DSB repair and genome maintenance.Cancer Signaling networks and Molecular Therapeutic