Naslov
The p53/p63/p73 family of proteins - the focus on isoforms and mutants in cancer

Autori
Slade, Neda ; Zorić, Arijana ; Horvat, Anđela

Izvornik
Periodicum biologorum (0031-5362) 112 (2010), 4; 425-432

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, pregledni rad, znanstveni

Ključne riječi
p53 ; p63 ; p73 ; tumorigenesis ; p53 mutations ; environmental carcinogen ; aristolochic acid ; endemic nephropaty

Sažetak
P53 tumor suppressor protein is critical for the cell growth control and the maintenance of genomic stability. These activities are due, at least in part, to its ability to form tetramers that bind to specificDNAsequences and activate transcription. Later discovered p53 homologues – p63 and p73 share remarkable structural and functional similarity with p53. All three genes have two promoters and undergo alternative splicing to generate multiple isoforms that might play important roles in carcinogenesis. Two groups of isoforms are generated: transactivating forms (p53/TAp63/TA73) with tumor suppressor activities as well as a number of amino-terminally truncated transactivation deficient isoforms (called DNp53/DNp63/DN73). It was recently discovered that p53, like p63 and p73, has a second internal promoter that leads to the synthesis of multiple isoforms whose function is not yet fully clear. Moreover, arising from alternative splicing of exons 6 to 9, new p53 splice variants were identified. In this review we describe different isoforms of p53, p63, p73 and their roles in tumorigenesis. Defining the interactions between p53/p63/p73 would give us new insight into the roles of these proteins in tumor formation. Mutations of the TP53 tumor suppressor gene have been found in nearly all tumor types and are estimated to contribute to more than 50% of all cancers. The study of p53 mutational spectra could give us clues about etiology of cancer. Recently, we reported the presence of specific p53 mutations in tumor tissue of patients from Croatia and Bosnia with endemic nephropathy. These data support the hypothesis that dietary exposure to AA is a major risk factor for endemic (Balkan) nephropathy.

Izvorni jezik
Engleski

Znanstvena područja
Biologija, Temeljne medicinske znanosti

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