All change: protein conformation and the ubiquitination reaction cascade

The structures of enzymes that collectively modify proteins by covalent addition of ubiquitin-like protein moieties have provided significant insights into the regulatory pathways they compose and have highlighted the importance of protein flexibility for the mechanism and regulation of the ubiquitination reaction

Analysis of the components of cancer risk perception and links with intention and behaviour: A UK-based study.

Funder: NIHR Academic Clinical FellowshipRisk perception refers to how individuals interpret their susceptibility to threats, and has been hypothesised as an important predictor of intentions and behaviour in many theories of health behaviour change. However, its components, optimal measurement, and effects are not yet fully understood. The TRIRISK model, developed in the US, conceptualises risk perception as deliberative, affective and experiential components. In this study, we aimed to assess the replicability of the TRIRISK model in a UK sample by confirmatory factor analysis (CFA), explore the inherent factor structure of risk perception in the UK sample by exploratory factor analysis (EFA), and assess the associations of EFA-based factors with intentions to change behaviour and subsequent behaviour change. Data were derived from an online randomised controlled trial assessing cancer risk perception using the TRIRISK instrument and intention and lifestyle measures before and after communication of cancer risk. In the CFA analysis, the TRIRISK model of risk perception did not provide a good fit for the UK data. A revised model developed using EFA consisted of two separate "numerical" and "self-reflective" factors of deliberative risk perception, and a third factor combining affective with a subset of experiential items. This model provided a better fit to the data when cross-validated. Using multivariable regression analysis, we found that the self-reflective and affective-experiential factors of the model identified in this study were reliable predictors of intentions to prevent cancer. There were no associations of any of the risk perception factors with behaviour change. This study confirms that risk perception is clearly a multidimensional construct, having identified self-reflective risk perception as a new distinct component with predictive validity for intention. Furthermore, we highlight the practical implications of our findings for the design of interventions incorporating risk perception aimed at behaviour change in the context of cancer prevention.This study was funded by the Cancer Research UK Prevention Fellowship (C55650/A21464). CR was supported by an NIHR Academic Clinical Fellowship. JC, WMPK and RAF received no specific funding for this project. JAUS was funded by the Cancer Research UK Prevention Fellowship (C55650/A21464)

Structural and functional characterization of Rpn12 identifies residues required for Rpn10 proteasome incorporation

The ubiquitin–proteasome system targets selected proteins for degradation by the 26S proteasome. Rpn12 is an essential component of the 19S regulatory particle and plays a role in recruiting the extrinsic ubiquitin receptor Rpn10. In the present paper we report the crystal structure of Rpn12, a proteasomal PCI-domain-containing protein. The structure helps to define a core structural motif for the PCI domain and identifies potential sites through which Rpn12 might form protein–protein interactions. We demonstrate that mutating residues at one of these sites impairs Rpn12 binding to Rpn10 in vitro and reduces Rpn10 incorporation into proteasomes in vivo

Tumour suppressors and oncogenes : Structure, function and drug design

EThOS - Electronic Theses Online ServiceGBUnited Kingdo

X-ray diffraction images for an MDM2/Nutlin-3a complex

<p>This submission includes a zip archive of diffraction images recorded with the MARMOSAIC 225 mm CCD detector at the ESRF beam line ID23-2. Relevant meta data can be found in the headers of those diffraction images or in the Protein Data Bank entry 4HG7.</p