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Review
. 2017 Mar;63(2):101-114.
doi: 10.18097/PBMC20176302101.

[Analysis of contribution of protein phosphorylation in the development of the diseases]

[Article in Russian]
M G Zavialova  1 , V G Zgoda  1 , E N Nikolaev  2
Affiliations
Review

[Analysis of contribution of protein phosphorylation in the development of the diseases]

[Article in Russian]
M G Zavialova et al. Biomed Khim. 2017 Mar.

Abstract
in English, Russian

In recent decades, studies in the molecular origins of socially significant diseases have made a big step forward with the development and using of high-performance methods in genomics and proteomics. Numerous studies in the framework of the global program "Human Proteome" were aimed at the identification of all possible proteins in various cell cultures and tissues, including cancer. One of the objectives was to identify biomarkers - proteins with high specificity to certain pathologies. However, in many cases, it is shown that the development of the disease is not associated with the appearance of new proteins, but depends on the level of gene expression or forming of proteoforms - splice variants, single amino acid substitutions (SAP variants), and post-translational modifications (PTM) of proteins. PTM may play a key role in the development of pathology because they activate a variety of regulatory or structural proteins in the majority of cell physiological processes. Phosphorylation is among the most significant of these protein modifications.This review will describe methods for analysis of protein phosphorylation used in the studies of such diseases as cancer and neurodegenerative diseases, as well as examples of cases when the modified proteins are involved directly to their development, and screening such significant PTM is used for the diagnosis and choice of treatment.

V poslednie desiatiletiia issledovaniia molekuliarnykh osnov razvitiia sotsial'no znachimykh zabolevaniĭ sdelali bol'shoĭ shag vpered blagodaria razvitiiu vysokoproizvoditel'nykh metodov genomiki i proteomiki. Mnogochislennye issledovaniia v ramkakh global'noĭ programmy “Proteom cheloveka” byli napravleny na identifikatsiiu vsekh vozmozhnykh belkov v razlichnykh kletochnykh kul'turakh i tkaniakh, v tom chisle i rakovykh. Odnoĭ iz tseleĭ bylo vyiavlenie tak nazyvaemykh biomarkerov – belkov, spetsificheskikh dlia opredelennykh patologiĭ. Odnako vo mnogikh sluchaiakh pokazano, chto razvitie zabolevaniia sviazano ne s poiavleniem novykh belkov, a zavisit ot urovnia ékspressii genov ili spetsificheskikh proteoform belkov – splaĭs-variantov, odinochnykh aminokislotnykh zamen (SAP) i post-transliatsionnykh modifikatsiĭ (PTM) belkov. PTM mogut igrat' kliuchevuiu rol' v razvitii patologii, potomu chto oni aktiviruiut razlichnye reguliatornye ili strukturnye belki v bol'shinstve kletochnykh fiziologicheskikh protsessov. Sredi takikh modifikatsiĭ naibolee znachimoĭ iavliaetsia fosforilirovanie. V dannom obzore rassmotreny metody analiza fosforilirovaniia, primeniaemye v issledovaniiakh molekuliarnykh osnov onkologicheskikh zabolevaniĭ, a takzhe privedeny primery, kogda modifitsirovannye belki vnosiat neposredstvennyĭ vklad v ikh razvitie. Skrining takikh znachimykh PTM primeniaetsia dlia diagnostiki i vybora metodov lecheniia.

Keywords: cancer; neurodegenerative diseases; phosphorylation; post-translational modifications (PTM); proteomics.

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