Protein p53 is one of the most studied proteins. This attention is primarily due to its key role in the cellular mechanisms associated with carcinogenesis. Protein p53 is a transcription factor involved in a wide variety of processes: cell cycle regulation and apoptosis, signaling inside the cell, DNA repair, coordination of metabolic processes, regulation of cell interactions, etc. This multifunctionality is apparently determined by the fact that p53 is a vivid example of how the same protein can be represented by numerous proteoforms bearing completely different functional loads. By alternative splicing, using different promoters and translation initiation sites, the TP53 gene gives rise to at least 12 isoforms, which can additionally undergo numerous (>200) post-translational modifications. Proteoforms generated due to numerous point mutations in the TP53 gene are adding more complexity to this picture. The proteoforms produced are involved in various processes, such as the regulation of p53 transcriptional activity in response to various factors. This review is devoted to the description of the currently known p53 proteoforms, as well as their possible functionality.
Belok p53 iavliaetsia odnim iz samykh izuchaemykh belkov. Po-vidimomu, takoe povyshennoe vnimanie k nemu vyzvano, prezhde vsego, ego kliuchevoĭ rol'iu v kletochnykh mekhanizmakh, sviazannykh s kantserogenezom. Belok r53 iavliaetsia transkriptsionnym faktorom, uchastvuiushchim v samykh raznoobraznykh protsessakh: reguliatsii kletochnogo tsikla i apoptoza, provedeniia signalov vnutri kletki, reparatsii DNK, koordinatsii metabolicheskikh protsessov, vzaimodeĭstviĭ mezhdu kletkami i t.d. Éta mnogofunktsional'nost', skoree vsego, opredeliaetsia tem, chto r53 mozhet byt' predstavlen v vide proteoform, nesushchikh sovershenno raznuiu funktsional'nuiu nagruzku. Putem al'ternativnogo splaĭsinga, ispol'zovaniia razlichnykh promotorov i saĭtov initsiatsii transliatsii gen TR53 daet nachalo ne menee 12 izoformam, kotorye dopolnitel'no mogut podvergat'sia mnogochislennym (>200) posttransliatsionnym modifikatsiiam. V étu slozhnuiu kartinu dobavliaiutsia eshche i proteoformy, kotorye obrazuiutsia za schet tochechnykh mutatsiĭ v gene TR53. Poluchennye v rezul'tate proteoformy uchastvuiut v razlichnykh protsessakh, takikh, naprimer, kak reguliatsiia transkriptsionnoĭ aktivnosti r53 v otvet na raznoobraznye faktory. Dannyĭ obzor i posviashchen opisaniiu izvestnykh na segodniashniĭ den' proteoform r53, a takzhe ikh vozmozhnoĭ funktsional'noĭ roli.
Keywords: gene; p53; proteoforms.