1,721,764 research outputs found
Carmine Melino and the Institute of Hygiene
No full textThroughout his 94 years of life, Carmine Melino brilliantly pursued different professional paths, his life being a constant stimulus for students, colleagues, friends and the family. Following the early formative years of study, here, we briefly list his scientific achievements in Occupational Medicine and Hygiene as well as his broad literary interests. Carmine was an inspiration to his generation not only because of his professional achievements, but also for his warm personality, exemplary hard playinglife and unbounded enthusiasm. A polymath, post-enlightenment ethos flowed to all his friends and colleagues, creating an ambience where intellectual excellence was highly appreciated and avidly pursued
MOLECULAR RECOGNITION MECHANISM OF p63 BY ITCH-E3 LIGASE: ADVANCES AND EFFECTS OF A p63 MUTATION RELATED TO ECTODERMAL DYSPLASIAS.
No full textRecently, it has been shown that Itch mediates the degradation of TAp63 and ΔNp63 proteins1. Itch E3–ligase contains four WW domains important in the recognized process. Several signalling complexes, that these domains mediate, have been implicated in human diseases (Muscular Dystrophy, Alzheimer's Disease, Huntington Disease etc.). WW domains are highly compact protein-protein binding modules that interact with short proline-rich sequences. Based on their ligand-binding specificity they have been categorized into four groups. WW domains fold into stable three-stranded antiparallel b-sheet structures, and their primary sequence share two conserved tryptophan residues spaced 20-22 amino acids apart. The four WW domains of Itch are considered belonging to the Group I, which binds polypeptides with a PY motif characterized by a PPXY consensus sequence, where X can be any residue. It is likely that the Itch-p63 interaction results from a direct interaction of Itch-WW2 domain with the PY motif of p63. Here, we present a structural characterization of the interaction by fluorescence, CD and NMR spectroscopy of the Itch-WW2 domain. Interaction studies in vitro between Itch-WW2 domain and pep63, which correspond to the fragment of the p63 protein including the PY motif, were performed. Moreover, the effects of a site specific mutation of p63, that has been reported in both Hay–Wells syndrome and Rapp–Hodgkin syndrome, was also evaluated both on the conformation of pep63 and on the WW-pep63 interaction.
1Rossi M., Aqeilan I., Neale M., Candi E., Salomoni P., Knight R.A., Croce C.M., Melino G. PNAS (2006) 103: 12753-5
P63 is a suppressor of tumorigenesis and metastasis interacting with mutant p53
No full textp53 mutations, occurring in two-thirds of all human cancers, confer a gain of function phenotype, including the ability to form metastasis, the determining feature in the prognosis of most human cancer. This effect seems mediated at least partially by its ability to physically interact with p63, thus affecting a cell invasion pathway, and accordingly, p63 is deregulated in human cancers. In addition, p63, as an 'epithelial organizer', directly impinges on epidermal mesenchimal transition, stemness, senescence, cell death and cell cycle arrest, all determinant in cancer, and thus p63 affects chemosensitivity and chemoresistance. This demonstrates an important role for p63 in cancer development and its progression, and the aim of this review is to set this new evidence that links p63 to metastasis within the context of the long conserved other functions of p63
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