LTI et Ordre du discours

Brossat Alain. LTI et Ordre du discours. In: Raison présente, n°167, 3e trimestre 2008. DEMONTER LE LANGAGE DU POUVOIR. pp. 51-57

Expression and regulatory network of E3 ubiquitin ligase NEDD4 family in cancers

Abstract NEDD4 family represent an important group of E3 ligases, which regulate various cellular pathways of cell proliferation, cell junction and inflammation. Emerging evidence suggested that NEDD4 family members participate in the initiation and development of tumor. In this study, we systematically investigated the molecular alterations as well as the clinical relevance regarding NEDD4 family genes in 33 cancer types. Finally, we found that NEDD4 members showed increased expression in pancreas cancer and decreased expression in thyroid cancer. NEDD4 E3 ligase family genes had an average mutation frequency in the range of 0-32.1%, of which HECW1 and HECW2 demonstrated relatively high mutation rate. Breast cancer harbors large amount of NEDD4 copy number amplification. NEDD4 family members interacted proteins were enriched in various pathways including p53, Akt, apoptosis and autophagy, which were confirmed by further western blot and flow cytometric analysis in A549 and H1299 lung cancer cells. In addition, expression of NEDD4 family genes were associated with survival of cancer patients. Our findings provide novel insight into the effect of NEDD4 E3 ligase genes on cancer progression and treatment in the future

Validation of the QTL for grain length linked to the Rht-B1 locus in two genetic backgrounds of bread wheat (Triticum aestivum L.)

Grain size is an important agronomic trait that influences the yield and end-use quality of bread wheat (Triticum aestivum L.). We conducted quantitative trait loci (QTL) analysis using recombinant inbred lines derived from a cross of a semi-dwarf modern variety with large grains (Zenkoujikomugi: Zen) and a landrace with small grains (Chinese Spring: CS). Grain size was evaluated as grain length (GL), grain width (GW), grain thickness (GT), and thousand-grain weight (TGW) under two environmental conditions. A major QTL (QGl.obu-4B) associated with GL was detected in both environments near the Rht-B1 locus for the semi-dwarf trait on chromosome 4B, despite Zen and CS having the same Rht-B1a allele. No QTL for GW was found in the QGl.obu-4B region, and QTLs for GT and TGW was detected in only one environment. To validate the effect of QGl.obu-4B, we developed two backcrossed populations in the CS and Zen genetic backgrounds. The Zen-derived allele conferred larger GL, GW, and GT, resulting in greater TGW (13.7% increase compared to the CS-derived allele) in the CS background. In contrast, the QGl.obu-4B effect was smaller in the Zen background, and the Zen-derived allele increased TGW by only 7.0%. The QTL was located within the 168-Mbp region tightly linked to the Rht-B1 locus. Further characterization and fine-mapping of QGl.obu-4B will facilitate the use of this allele by marker-assisted selection in wheat breeding programs

DNA Methylation Correlates with the Expression of Drought-Responsive Genes and Drought Resistance in Rice

The δ13C value is regarded as an important indicator for tolerance to drought stress (DS), which is a severe abiotic stress that influences rice productivity. However, exploration of drought-responsive genes (DRGs) related to δ13C regulation is less reported. In this study, we investigated the natural variation in δ13C values in 102 japonica rice accessions. Among them, two rice accessions with contrasting δ13C values, Longdao 10 (LD10, DS-tolerant) and Binxu (BX, DS-sensitive), were used for further analysis. LD10 possesses better drought resistance with 2% lower δ13C values, 35% lower stomatal length and density, 33% lower water loss, and 11% lower stomatal conductance in comparison to BX. Transcriptome analysis shows that there are 2325 and 1378 differentially expressed genes (DEGs) induced by DS in LD10 and BX at the tillering stage, respectively, while there are 1076 and 492 DEGs in LD10 and BX at the graining stage, respectively. In total, 21 overlapped DEGs (defined as DRGs) were identified due to DS effects across two rice accessions over two stages. Among them, the expression levels of six genes, including chloride transporter (CLT1) and photosystem II polypeptide (PSBP), were further tested using qRT-PCR. Furthermore, we found that four methyltransferase genes were upregulated in BX compared to LD10 under DS. Consistently, the methylation levels of CLT1 and PSBP were higher along both promoter and CDS regions for CG, CHG, and CHH types. This study highlights the importance of the expression of these DRGs in response to DS and provides deep insights into DNA methylation-driven gene expression conferring different drought responses in rice

The phosphorylation-deubiquitination positive feedback loop of the CHK2-USP7 axis stabilizes p53 under oxidative stress

Summary: p53 regulates multiple signaling pathways and maintains cell homeostasis under conditions of DNA damage and oxidative stress. Although USP7 has been shown to promote p53 stability via deubiquitination, the USP7-p53 activation mechanism has remained unclear. Here, we propose that DNA damage induces reactive oxygen species (ROS) production and activates ATM-CHK2, and CHK2 then phosphorylates USP7 at S168 and T231. USP7 phosphorylation is essential for its deubiquitination activity toward p53. USP7 also deubiquitinates CHK2 at K119 and K131, increasing CHK2 stability and creating a positive feedback loop between CHK2 and USP7. Compared to peri-tumor tissues, thyroid cancer and colon cancer tissues show higher CHK2 and phosphorylated USP7 (S168, T231) levels, and these levels are positively correlated. Collectively, our results uncover a phosphorylation-deubiquitination positive feedback loop involving the CHK2-USP7 axis that supports the stabilization of p53 and the maintenance of cell homeostasis