Members of the evolutionarily conserved Mastermind (MAM) protein family, including the three related mammalian Mastermind-like (MAML) proteins MAML1-3, function as crucial coactivators of Notch-mediated transcriptional activation. Given the recent evidence of cross-talk between the p53 and Notch signal transduction pathways, we have investigated whether MAML1 may also be a transcriptional coactivator of p53. Indeed, we show here that MAML1 is able to interact with p53. We show that MAML1-p53 interaction involves the N-terminal region of MAML1 and the DNA-binding domain of p53, and we use a chromatin immunoprecipitation assay to show that MAML1 is part of the activator complex that binds to native p53-response elements within the promoter of the p53 target genes. Overexpression of wild-type MAML1 as well as a mutant, defective in Notch signaling, enhanced the p53-dependent gene induction in mammalian cells, whereas MAML1 knockdown reduced the p53-dependent gene expression. MAML1 increases the half-life of p53 protein and enhances its phosphorylation/acetylation upon DNA damage of cells. Finally, RNA interference-mediated knockdown of the single Caenorhabditis elegans MAML homolog, Lag-3, led to substantial abrogation of p53-mediated germ-cell apoptotic response to DNA damage and markedly reduced the expression of Ced-13 and Egl-1, downstream pro-apoptotic targets of the C. elegans p53 homolog Cep-1. Thus, we present evidence for a novel coactivator function of MAML1 for p53, independent of its function as a coactivator of Notch signaling pathway.
Background and study aims Endoscopic ultrasound-directed transgastric ERCP (EDGE) is a new endoscopic procedure to perform ERCP in Roux-en-y gastric bypass (RYGB) patients. The aim of this study was to conduct a systematic review and meta-analysis to evaluate technical success, clinical success and adverse effects of EDGE and compare it to laparoscopic ERCP (LA-ERCP) and balloon ERCP (BE-ERCP).
Patients and methods We conducted a comprehensive search of several databases and conference proceedings including PubMed, EMBASE, Google-Scholar, LILACS, SCOPUS, and Web of Science databases to identify studies reporting on EDGE, LA-ERCP, and BE-ERCP. The primary outcome was to evaluate technical and clinical success of all three procedures and the secondary analysis focused on calculating the pooled rate of all adverse events (AEs), along with the commonly reported AE subtypes.
Results Twenty-four studies on 1268 patients were included in our analysis with the majority of the population being males with mean age 53.72 years. Pooled rates of technical and clinical success with EDGE wer 95.5 % and 95.9 %, with LA-ERCP were 95.3 % and 92.9 % and were BE-ERCP were 71.4 % and 58.7 %, respectively. Pooled rates of all AEs with EDGE were 21.9 %, with LA-ERCP 17.4 % and with BE-ERCP 8.4 %. Stent migration was the most common AE with EDGE with 13.3 % followed by bleeding with 6.6 %.
Conclusion Our meta-analysis demonstrated that the technical and clinical success of EDGE procedure is better than BE-ERCP and comparable to that of LA-ERCP in RYGB patients. EDGE also has a similar safety profile as compared to LA-ERCP but has higher AE rate as compared to BE-ERCP.
We study modulation instability (MI) of flat states in two-component spin-orbit-coupled (SOC) Bose-Einstein condensates (BECs) in the framework of coupled Gross-Pitaevskii equations for two components of the pseudo-spinor wave function. The analysis is performed for equal densities of the components. Effects of the interaction parameters, Rabi coupling and SOC on the MI are investigated. In particular, the results demonstrates that the SOC strongly alters the commonly known MI (immiscibility) condition, g 2 12 > g1g2, for the binary superfluid with coefficients g1,2 and g12 of the intra-and inter-species repulsive interactions. In fact, the binary BEC is always subject to the MI under the action of the SOC, which implies that ground state of the system is plausibly represented by a striped phase.
Biochemical mechanisms that control the levels and function of key tumor suppressor proteins are of great interest as their alterations can lead to oncogenic transformation. Here, we identify the human orthologue of Drosophila melanogaster ecdysoneless (hEcd) as a novel p53-interacting protein. Overexpression of hEcd increases the levels of p53 and enhances p53 target gene transcription whereas hEcd knockdown has the opposite effects on p53 levels and target gene expression. Furthermore, hEcd interacts with murine double minute-2 and stabilizes p53 by inhibiting murine double minute-2-mediated degradation of p53. Thus, hEcd protein represents a novel regulator of p53 stability and function. Our studies also represent the first demonstration of a biochemical function for hEcd protein and raise the possibility that altered hEcd levels and/or function may contribute to oncogenesis.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.