Learn 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)
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)
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)
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)
Arf and p53 are regarded among the most relevant tumor suppressors based on their ubiquitous and frequent inactivation in human cancer. The Arf/p53 pathway protects cells against several types of damage and this is the basis of its tumor suppressor activity. Interestingly, aging is a process associated with the accumulation of damage derived from chronic(More)
Many studies have positioned Notch signaling at various critical junctions during T-cell development. There is, however, debate regarding the role of Notch in the CD4 versus CD8 lineage commitment. Because there are 4 Notch receptors and RBP-Jkappa-independent Notch signaling has been reported, we decided to eliminate gamma-secretase activity once its(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), a member of the Birnaviridae family, is the causative agent of one of the most important infectious poultry diseases. Major aspects of the molecular biology of IBDV, such as assembly and replication, are as yet poorly understood. We have previously shown that encapsidation of the putative virus-encoded RNA-dependent(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.