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Cellular senescence disables proliferation in damaged cells, and it is relevant for cancer and aging. Here, we show that senescence occurs during mammalian embryonic development at multiple locations, including the mesonephros and the endolymphatic sac of the inner ear, which we have analyzed in detail. Mechanistically, senescence in both structures is(More)
Telomerase confers limitless proliferative potential to most human cells through its ability to elongate telomeres, the natural ends of chromosomes, which otherwise would undergo progressive attrition and eventually compromise cell viability. However, the role of telomerase in organismal aging has remained unaddressed, in part because of the(More)
The tumour-suppressor pathway formed by the alternative reading frame protein of the Cdkn2a locus (Arf) and by p53 (also called Trp53) plays a central part in the detection and elimination of cellular damage, and this constitutes the basis of its potent cancer protection activity. Similar to cancer, ageing also results from the accumulation of damage and,(More)
Regulatory T (T reg) cells exert powerful down-modulatory effects on immune responses, but it is not known how they act in vivo. Using intravital two-photon laser scanning microscopy we determined that, in the absence of T reg cells, the locomotion of autoantigen-specific T cells inside lymph nodes is decreased, and the contacts between T cells and(More)
T cells + CD8 Effect of Presenilins in the apoptosis of thymocytes and homeostasis of (4939 articles) Immunobiology (746 articles) Apoptosis Articles on similar topics can be found in the following Blood collections Information about subscriptions and ASH membership may be found online at: digital object identifier (DOIs) and date of initial publication.(More)
Missense mutations in TP53 gene promote metastasis in human tumours. However, little is known about the complete loss of function of p53 in tumour metastasis. Here we show that squamous cell carcinomas generated by the specific ablation of Trp53 gene in mouse epidermis are highly metastatic. Biochemical and genome-wide mRNA and miRNA analyses demonstrated(More)
Infectious bursal disease virus (IBDV) capsids are formed by a single protein layer containing three polypeptides, pVP2, VP2, and VP3. Here, we show that the VP3 protein synthesized in insect cells, either after expression of the complete polyprotein or from a VP3 gene construct, is proteolytically degraded, leading to the accumulation of product lacking(More)
Our results open a new therapeutic opportunity to treat NSCLC using GSIs. Interestingly, GSIs have been used in long-term treatments in Alzheimer´s patients without major side effects (although without improving the course of the disease). The accumulated knowledge on the pharmacology of GSIs should pave the way to test these compounds in NSCLC patients.
Notch signaling is essential for the development of T cell progenitors through the interaction of NOTCH1 receptor on their surface with the ligand, Delta-like 4 (DLL4), which is expressed by the thymic epithelial cells. Notch signaling is quickly shut down once the cells pass β-selection, and CD4/CD8 double positive (DP) cells are unresponsive to Notch.(More)
The implication of the Notch pathway in cancer has been known since it was found hyperactivated in acute T-cell lymphoblastic leukemias (TALL) one decade ago. During this time, the link between the Notch pathway and cancer has been extended to many types of malignancies. A unique feature of the pathway is the fact that it can be oncogenic or tumor(More)