Contribution of the different modules in the utrophin carboxy-terminal region to the formation and regulation of the DAP complex

AbstractThe carboxy-terminal region of utrophin, like the homologous proteins dystrophin, Drp2 and dystrobrevins, contains structural domains frequently involved in protein–protein interaction. These domains (WW, EF hands, ZZ and H1–H2) mediate recognition and binding to a multicomponent complex of proteins, also known as dystrophin-associated proteins (DAPs) for their association with dystrophin, the product of the gene, mutated in Duchenne muscular dystrophy. We have exploited phage display and in vitro binding assays to study the recognition specificity of the different domains of the utrophin carboxy-terminus. We found that none of the carboxy-terminal domains of utrophin, when isolated from its structural context, selects specific ligand peptides from a phage-displayed peptide library. By contrast, panning with an extended region containing the WW, EF hands, and ZZ domain defines the consensus binding motif, PPxY which is also found in β-dystroglycan, a component of the DAP complex that interacts with utrophin in several tissues. WW-mediated binding to PPxY peptides and to β-dystroglycan requires the presence of the EF hands and ZZ domain. When the ZZ domain is either deleted or engaged in binding to calmodulin, the utrophin β-dystroglycan complex cannot be formed. These findings suggest a potential regulatory mechanism by means of which the attachment of utrophin to the DAP complex can be modulated by the Ca2+-dependent binding of calmodulin. The remaining two motifs found in the carboxy-terminus (H1–H2) mediate the formation of utrophin–dystrobrevin hybrids but do not select ligands in a repertoire of random nonapeptides

CommonSpaces: an approach to web learning based on OERs, mentoring and collaborative learning

[EN] Currently, the internet is full of freely accessible resources that can provide excellent learning opportunities. However, these resources are usually not well organized, and for many users it is often difficult to use these dispersed sources of knowledge in a coordinated way. The project CommonS aims at building a space - called CommonSpaces - dedicated to communities of practice in which participants learn through the cataloguing, re-use, adaptation and sequencing of Open Educational Resources (OERs) into socalled learning paths. We define a Learning Path as an organized set of interconnected OERs (created by communities of users) that can be created by users both to organize their learning experience and to provide consistent learning sequences for others. In this paper, we briefly present the rationale and the theoretical foundations of the project. Then we discuss the features of CommonSpaces in its first prototype version and describe the preliminary findings from a pioneering experience of collaborative learning carried out by means of CommonSpaces. We conclude discussing the ongoing collective modeling of the final version of CommonSpaces and its future directions.Lariccia, S.; Ritella, G.; Montanari, M.; Cesareni, D.; Toffoli, G. (2016). CommonSpaces: an approach to web learning based on OERs, mentoring and collaborative learning. En 2nd. International conference on higher education advances (HEAD'16). Editorial Universitat Politècnica de València. 326-333. https://doi.org/10.4995/HEAD16.2015.2733OCS32633

Physical interaction with Yes-associated protein enhances p73 transcriptional activity.

Specific protein-protein interactions are involved in a large number of cellular processes and are mainly mediated by structurally and functionally defined domains. Here we report that the nuclear phosphoprotein p73 can engage in a physical association with the Yes-associated protein (YAP). This association occurs under physiological conditions as shown by reciprocal co-immunoprecipitation of complexes from lysates of P19 cells. The WW domain of YAP and the PPPPY motif of p73 are directly involved in the association. Furthermore, as required for ligands to group I WW domains, the terminal tyrosine (Y) of the PPPPY motif of p73 was shown to be essential for the association with YAP. Unlike p73alpha, p73beta, and p63alpha, which bind to YAP, the endogenous as well as exogenously expressed wild-type p53 (wt-p53) and the p73gamma isoform do not interact with YAP. Indeed, we documented that YAP interacts only with those members of the p53 family that have a well conserved PPXY motif, a target sequence for WW domains. Overexpression of YAP causes an increase of p73alpha transcriptional activity. Differential interaction of YAP with members of the p53 family may provide a molecular explanation for their functional divergence in signaling

Physical and Functional Interaction between p53 Mutants and Different Isoforms of p73

p53 is the most frequently inactivated tumor suppressor gene in human cancer, whereas its homologue, p73, is rarely mutated. Similarly to p53, p73 can promote growth arrest or apoptosis when overexpressed in certain p53-null tumor cells. It has previously been shown that some human tumor-derived p53 mutants can exert gain of function activity. The molecular mechanism underlying this activity remains to be elucidated. We show here that human tumor-derived p53 mutants (p53His175 and p53Gly281) associate in vitro and in vivo with p73 alpha, beta, gamma, and delta. This association occurs under physiological conditions, as verified in T47D and SKBR3 breast cancer cell lines. The core domain of mutant p53 is sufficient for the association with p73, whereas both the specific DNA binding and the oligomerization domains of p73 are required for the association with mutant p53. Furthermore, p53His175 and p53Gly281 mutants markedly reduce the transcriptional activity of the various isoforms of p73. Thus, human tumor-derived p53 mutants can associate with p73 not only physically but also functionally. These findings define a network involving mutant p53 and the various spliced isoforms of p73 that may confer upon tumor cells a selective survival advantage

Making decisions in G1

[No abstract available

Finally: The digital, democratic age of scientific abstracts

[No abstract available

Protein interactions: integration leads to belief

[No abstract available

Searching the MINT Database for Protein Interaction Information

The Molecular Interactions Database (MINT) is a relational database designed to store information about protein interactions. Expert curators extract the relevant information from the scientific literature and deposit it in a computer readable form. Currently (April 2008), MINT contains information on almost 29,000 proteins and more than 100,000 interactions from more than 30 model organisms. This unit provides protocols for searching MINT over the Internet, using the MINT Viewer. © 2008 by John Wiley & Sons, Inc

CommonSpaces: an approach to web learning based on OERs, mentoring and collaborative learning

Currently, the internet is full of freely accessible resources that can provide excellent learning opportunities. However, these resources are usually not well organized, and for many users it is often difficult to use these dispersed sources of knowledge in a coordinated way. The project CommonS aims at building a space -called CommonSpaces -dedicated to communities of practice in which participants learn through the cataloguing, re-use, adaptation and sequencing of Open Educational Resources (OERs) into so-called learning paths. We define a Learning Path as an organized set of interconnected OERs (created by communities of users) that can be created by users both to organize their learning experience and to provide consistent learning sequences for others. In this paper, we briefly present the rationale and the theoretical foundations of the project. Then we discuss the features of CommonSpaces in its first prototype version and describe the preliminary findings from a pioneering experience of collaborative learning carried out by means of CommonSpaces. We conclude discussing the ongoing collective modeling of the final version of CommonSpaces and its future directions. CommonSpaces: an approach to web learning based on OERs, mentoring and collaborative learnin