Structural basis of high-order oligomerization of the cullin-3 adaptor SPOP.

Protein ubiquitination in eukaryotic cells is mediated by diverse E3 ligase enzymes that each target specific substrates. The cullin E3 ligase complexes are the most abundant class of E3 ligases; they contain various cullin components that serve as scaffolds for interaction with substrate-recruiting adaptor proteins. SPOP is a BTB-domain adaptor of the cullin-3 E3 ligase complexes; it selectively recruits substrates via its N-terminal MATH domain, whereas its BTB domain mediates dimerization and interactions with cullin-3. It has recently been recognized that the high-order oligomerization of SPOP enhances the ubiquitination of substrates. Here, a dimerization interface in the SPOP C-terminus is identified and it is shown that the dimerization interfaces of the BTB domain and of the C-terminus act independently and in tandem to generate high-order SPOP oligomers. The crystal structure of the dimeric SPOP C-terminal domain is reported at 1.5 Å resolution and it is shown that Tyr353 plays a critical role in high-order oligomerization. A model of the high-order SPOP oligomer is presented that depicts a helical organization that could enhance the efficiency of substrate ubiquitination

The Tnt1 Retrotransposon Escapes Silencing in Tobacco, Its Natural Host

Retrotransposons' high capacity for mutagenesis is a threat that genomes need to control tightly. Transcriptional gene silencing is a general and highly effective control of retrotransposon expression. Yet, some retrotransposons manage to transpose and proliferate in plant genomes, suggesting that, as shown for plant viruses, retrotransposons can escape silencing. However no evidence of retrotransposon silencing escape has been reported. Here we analyze the silencing control of the tobacco Tnt1 retrotransposon and report that even though constructs driven by the Tnt1 promoter become silenced when stably integrated in tobacco, the endogenous Tnt1 elements remain active. Silencing of Tnt1-containing transgenes correlates with high DNA methylation and the inability to incorporate H2A.Z into their promoters, whereas the endogenous Tnt1 elements remain partially methylated at asymmetrical positions and incorporate H2A.Z upon induction. Our results show that the promoter of Tnt1 is a target of silencing in tobacco, but also that endogenous Tnt1 elements can escape this control and be expressed in their natural host

Hallazgos colonoscópicos del estudio piloto de cribado de cáncer colorrectal realizado en Cataluña Colonoscopic findings from a pilot screening study for colorectal cancer in Catalonia

Objetivo: evaluar las lesiones detectadas en las dos rondas ya finalizadas del Programa Piloto de Cribado en Cáncer Colorrectal (CCR) llevado a cabo en L'Hospitalet de Llobregat (Barcelona). Material y métodos: el programa de cribado de CCR se inició en el año 2000. La población, comprendida entre 50 y 69 años residentes en el área, fue invitada a participar a través de la determinación bienal de sangre oculta en heces mediante el test guaiaco y colonoscopia en los participantes con test positivo. Se realizó polipectomía de las lesiones detectadas o biopsias cuando no era posible la extirpación. Los pólipos se clasificaron según criterios de la Organización Mundial de la Salud. Resultados: se realizaron 442 colonoscopias de los 495 test positivos. En 213 individuos, se detectaron: 36 cánceres invasivos, 121 adenomas de alto riesgo, 29 adenomas de bajo riesgo y 27 pólipos hiperplásicos. En el 25,8% de los casos, el tamaño de los adenomas fue Objective: to evaluate lesions detected in two screening rounds performed in a pilot screening program for colorectal cancer in Catalonia, Spain. Material and methods: a colorectal cancer screening program was initiated in 2000. The target population included men and women aged 50-69 years. Screening consisted of biennial guaiac-based fecal occult blood testing (FOBT), and colonoscopy for participants with a positive FOBT. Any polyps found were removed, and biopsies were performed for any masses. Results: Colonoscopies were performed in 442 of 495 people with positive FOBT. In 213 (48.2%), 36 invasive cancers, 121 high-risk adenomas, 29 low-risk adenomas, and 27 hyperplastic polyps were diagnosed. Lesion size was smaller than 10 mm in 25.8% of cases. Most detected lesions (37.2%) were located in the distal colon, followed by the proximal colon (5.7%) and both locations (5.2%). Advanced neoplasm was significantly associated with male gender and distal location. The prevalence of advanced proximal neoplasms among patients with no distal polyps was 5.1%. Conclusions: the most common lesions detected by colonoscopy were high-risk adenomas located in the distal colon. FOBT is a suitable method for detecting small precancer lesions during population screening, and is thus a key factor in reducing the incidence of colorectal cancer