Cancer-causing HPV E6 oncoproteins are characterized by the presence of a PDZ binding motif (PBM) at their extreme carboxy terminus. It was long thought that this region of E6 had a sole function to confer interaction with a defined set of cellular substrates. However, more recent studies have shown that the E6 PBM has a complex pattern of regulation, whereby phosphorylation within the PBM can regulate interaction with two classes of cellular proteins: those containing PDZ domains and the members of the 14-3-3 family of proteins. In this review, we explore the roles that the PBM and its ligands play in the virus life cycle, and subsequently how these can inadvertently contribute towards the development of malignancy. We also explore how subtle alterations in cellular signal transduction pathways might result in aberrant E6 phosphorylation, which in turn might contribute towards disease progression.

Autoantibodies related to APLS (aCL and aβ2GPI) were present in the majority of patients with PBC, reflecting the ability of these antibodies to engage mediators of damage.

Anti-Saccharomyces cerevisiae antibodies (ASCA) had been known to be specific for Crohn's disease but it has been found in many other autoimmune diseases like systemic lupus erythematosus (SLE). Furthermore, cross-reactive epitopes on β2-glycoprotein I (β2GPI) and Saccharomyces cerevisiae were found in SLE patients. The aims of this study were to evaluate the frequency of ASCA in patients with SLE and to compare it with that of anti-β2GPI antibodies (aβ2GPI). Sera of 116 patients with SLE were analyzed in this retrospective study. All patients fulfilled at least 4 criteria of the 1997 American College of Rheumatology updated criteria for the classification of SLE. Sera of 160 blood donors were included as normal controls. ASCA IgA and IgG and aβ2GPI antibodies were determined by enzyme-linked immunosorbent assays. The frequency of ASCA (IgG and/or IgA) was significantly higher in SLE patients than in control group (31.9 vs. 3.7 %, p < 10(-6)). ASCA IgG and ASCA IgA were more frequent in SLE patients than in control group (29.3 vs. 3.1 %, p < 10(-6) and 12.1 vs. 0.6 %, p = 10(-4), respectively). The mean level of ASCA IgG was higher than that of ASCA IgA (9.5 vs. 6.4 U/ml) but the difference was not statistically significant. The frequencies of aβ2GPI (IgG and/or IgA) and aβ2GPI IgA were significantly higher than those of ASCA (IgG and/or IgA) and ASCA IgA (54.3 vs. 31.9 %, p = 5 × 10(-4) and 50.9 vs. 12.1 %, p < 10(-6), respectively). Increased ASCA IgG was observed in patients with SLE, suggesting a role of environmental stimuli in its pathogenesis.

Patients with GD had a higher frequency of ASCA IgG than controls.

Association between pectus excavatum and congenital genetic disorders: a systematic review and practical guide for the treating physician,