Staying under the radar - the multifunctional LANA Protein

Many viruses have developed numerous strategies to recruit and take advantage of cellular protein degradation pathways to evade the cellular viral immune system. One such virus is the Kaposi´s Sarcoma associated herpesvirus (KSHV), first discovered in Kaposi´s Sarcoma lesions found in AIDS patients. Latency-Associated Nuclear Antigen (LANA) is a KSHV multifunctional protein responsible for tethering viral DNA to the chromosome ensuring maintenance and segregation of the viral genome during cell division. Besides its main role of viral maintenance, LANA also physically interacts with several host proteins to modulate cell functions. One such function is to recruit the EC5S ubiquitin-ligase complex by interacting with Elongin BC complex and Cullin 5 protein, which in turn ubiquitinate substrates such as NF-κB and p53 to allow persistent viral infection. Like any other post-translation modifications, ubiquitination is reversible through deubiquitination enzymes (DUBs). LANA also interacts with ubiquitin specific protease 7 (USP7), a deubiquitination enzyme involved in regulation of several proteins including p53. Interaction with USP7 is made through a conserved peptide motif, which is also present in LANA. This work addresses the role of LANA in the recruitment and modulation of the ubiquitination and deubiquitination pathways. Despite the continued efforts in uncovering new LANA interacting partners to form a functional EC5S ubiquitin-ligase complex, only MHV-68 LANA interacted directly with Elongin BC, other interactions were not direct and may require a linker protein. On the other hand, LANA interaction with USP7 was able to be analysed by X-ray structure determination. In addition to a conserved P/AxxS motif, a novel Glutamine (Gln) residue from KSHV LANA was shown to make a specific interaction with USP7. This Gln residue is also present in other herpesvirus protein and hence it might be a conserved motif within herpesviruses.

O serviço fiscal aduaneiro criminal e contraordenacional da GNR

At a time of global economic instability, to which Portugal is not oblivious, and aware that the main source of Portuguese State revenue relies on the collection of tribute, the National Republican Guard holds within its mission relevant assignments to the protection of the financial interests of the country, in particular, fiscal and customs. These assignments were inherited from the century - old institution Guarda Fiscal - with evidence given in this domain, which was integrated into the National Republican Guard in 1993, to adopt, a 1St model, that held a specialized unit – Brigada Fiscal, with surveillance and patrolling missions of costa and fiscal and customs supervision, throughout the national territory and maritime zone of respect. In 2009, the result of political decisions, reorganization the State's central administration, appears de 2Nd model, because the Brigada Fiscal assignments were divided by two specialized units - UAF with investigation skills, and UCC for patrolling and surveillance of the coast. Analyzed the legal spectrum of special legislation leading the criminal and transgression sector punitive (RGIT), in essence, is in the UAF that resides the role assignments from the scope of the investigation and supervision of goods in the national territory on a par with the tax authority. Tax inspection assignments, fiscal and customs of the National Republican Guard, are unmatched in the National Tribute System, constituting itself as a potentiality of this special body, in similarity of their counterparts - Spain and Italy; however, have some constraints, that urge to clarify and repair. Foreseeing the future, face the announced news of a new restructuring, on behalf of the interests of the country, and in order to raise the quality of performance of the tax inspection, fiscal and customs, the National Republican Guard shall maintain a model based on the experience already accumulated, obviously adapted to the new demands of a changing society. Despite the current model gain in efficiency, loses in effectiveness. However, the efficiency of a model, without the necessary resources, can never bring “the letter to Garcia” against any kind of infringements, criminal or transgressions. Unless better opinion, both tax structures of the National Republican Guard are valid as an instrument for the prevention and combat of these illegal types. Because they are strategic in pursuing the public interest, given the scarce resources of the country and be the National Republican Guard, the force with the means and know-how of this nature. The political power has the final word.