Procédure informatisée de soins en médecine générale sur l'antibiothérapie probabiliste dans les principales infections communautaires urologiques, génitales, digestives et cutanées de l'adulte

GRENOBLE1-BU Médecine pharm. (385162101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Nucleo-cytoplasmic shuttling of high risk human Papillomavirus E2 proteins induces apoptosis.

Human Papillomavirus (HPV) E2 proteins are the major viral regulators of transcription and replication during the viral life cycle. In addition to these conserved functions, we show that E2 proteins from high risk HPV types 16 and 18, which are associated with cervical cancer, can induce apoptosis. In contrast, E2 proteins from low risk HPV types 6 and 11, which are associated with benign lesions, do not cause cell death. We show that the ability to induce apoptosis is linked to the intracellular localization of the respective E2 proteins rather than to inherent properties of the proteins. Although low risk HPV E2 proteins remain strictly nuclear, high risk HPV E2 proteins are present in both the nucleus and the cytoplasm of expressing cells due to exportin-1 receptor (CRM1)-dependent nucleo-cytoplasmic shuttling. Induction of apoptosis is caused by accumulation of E2 in the cytoplasm and involves caspase 8 activation. We speculate that disruption of the E2 gene during viral genome integration in cervical carcinoma provides a means to avoid E2-induced apoptosis and allow initiation of carcinogenesis

High-risk but not low-risk HPV E2 proteins bind to the APC activators Cdh1 and Cdc20 and cause genomic instability.

Human papillomaviruses (HPVs) from the high-risk group are associated with cervical cancer, in contrast to HPVs from the low-risk group which are associated with benign lesions of the genital tract. Here, we show that high-risk, but not low-risk HPV E2 proteins, promote a mitotic block, often followed by metaphase-specific apoptosis, and which is independent of the viral oncogenes E6 and E7. High-risk HPV E2-expressing cells also show polyploidy, chromosomal mis-segregation and centrosome amplification leading to genomic instability. We link these defects to a specific and unusually strong interaction between high-risk E2 and both Cdc20 and Cdh1, two activators of the Anaphase Promoting Complex (APC), abnormal localization of Cdh1, and accumulation of APC substrates like cyclin B, in vivo. The finding that high-risk, but not low-risk HPV E2 proteins, induce genomic instability, raises the intriguing possibility that E2 proteins play a role in the oncogenic potential of high-risk papillomaviruses

The Interactome of Soybean GmWRKY53 using Yeast 2-Hybrid Library Screening to Saturation

Soybean GmWRKY53 functions in both biotic and abiotic stress signaling. Using GmWRKY53 as a bait yeast 2-hybrid library screening to saturation isolated multiple independent fragments for many interacting proteins, enabling delineation of minimal interacting domains and computation of a confidence score. Multiple independent clones coding for the LATE ELONGATED HYPOCOTYL clock protein GmLCL2 (MYB114) were isolated and the binding site for GmWRKY53 was mapped to 90 amino acids separate from the MYB domain. This suggests a direct input from the clock on GmWRKY53 activity. The GmWRKY53-interacting proteins also included 3 water stress-inducible AP2/ERF transcription factors. One of these (Glyma03g26310) is one of the most strongly water stress induced genes in soybean roots, suggesting that GmWRKY53/ERF complexes regulate water stress responses