Sirtuin1-3 Deasetilazlar: Biyolojik Fonksiyonları ve Kanserde Terapötik Potansiyelleri

Year 2022, Volume: 12 Issue: 2, 1055 - 1069, 01.06.2022

Selma Yıldırım Ramazan Demirel Meryem İçen Özkan Özden

https://doi.org/10.21597/jist.987658

Abstract

Dünya üzerinde en ölümcül hastalıklar listesinde kalp-damar hastalıklarından sonra ikinci sırada yer alan kanser, genel olarak yaşla birlikte görülme sıklığı artan bir hastalık grubudur. Bununla birlikte, son yıllarda genç hastalarda da görülme sıklığının artması, araştırmacıları yeni ve alternatif tedavi arayışlarına yönlendirmektedir. Mayadaki Sir2 geninin memelilerdeki homologları olan sirtuin (SIRT) deasetilaz ailesi, tip 2 diyabet, obezite, kalp-damar hastalıkları, bazı sinir hastalıkları ve kanser gibi yaşlanmayla birlikte görülme sıklığı artan birçok hastalığın ortaya çıkmasıyla ilişkilendirilmesi, son yıllarda bu enzimlerin biyolojik rollerinin anlaşılmasına olan ilgiyi arttırmıştır. SIRT’ler DNA onarımı, apoptozis, metabolizma ve yaşlanma gibi hücresel olayların düzenlenmesindeki rolleri nedeniyle kanser tedavisinde yeni yaklaşımlar sunmaktadır. Nikotinamid adenin dinükleotide (NAD+) bağımlı Sınıf III histon deasetilazlar olarak da bilinen bu proteinlerin aktivitesini özel SIRT aktivatör ve inhibitörlerle değiştirilmesi mümkündür. Bu derlemede, SIRT proteinlerinin en çok çalışılan üç üyesi SIRT1, SIRT2 ve SIRT3’ün biyolojik rolleri, kanser ile olan ilişkileri ve SIRT’lerin aktivitelerini değiştiren yeni organik moleküllerin kanser tedavisindeki önemini araştıran güncel araştırma makaleleri derlenmiş ve Türkçe literatür eksikliğini gidermeye katkı sağlamayı amaçlanmıştır.

Keywords

Kanser, sirtuin, nikotinamid adenin dinükleotid (NAD+), apoptozis, DNA onarımı

Supporting Institution

TÜBİTAK

Project Number

120C117

Thanks

Bu derlemenin sorumlu yazarı 2247-A TÜBİTAK Ulusal Öncü Araştırmacılar programı (proje #120C117) ile desteklenmektedir.

Sirtuin 1-3 Deacetylases: Biological Functions and Therapeutic Potential in Cancer

Abstract

Cancer, which ranks second in the list of the deadliest diseases in the world after cardiovascular diseases, is a group of diseases whose incidence increases with age. However, the increased incidence in young patients in recent years has led researchers to search for novel and alternative treatments. The fact that members of the sirtuin (SIRT) deacetylase family, which are mammalian homologues of the Sir2 gene in yeast, have important roles in the occurrence and treatment of aging-related diseases, such as type 2 diabetes, obesity, cardiovascular disease and cancer, has amplified interest to the understanding of the roles of these enzymes in recent years. SIRTs offer novel approaches in cancer treatment by regulating cellular events, such as DNA repair, apoptosis, metabolism, and aging. It is possible to alter the activity of these proteins, also known as nicotinamide adenine dinucleotide (NAD+) dependent Class III histone deacetylases, with specific SIRT activators and inhibitors. In this review, the biological roles of the three most studied members of SIRT proteins, SIRT1, SIRT2 and SIRT3, and the importance of new organic molecules that change the activities of these SIRTs in cancer treatment in the light of recent literature are discussed, and it was aimed to contribute to filling the lack of Turkish literature on this subject.

Keywords

Cancer, sirtuin, nicotinamide adenine dinucleotide (NAD+), apoptosis, DNA repair

Project Number

120C117

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