Otofaji ile İlişkili Bazı Genlerdeki Androjen Cevap Elementlerinin İn Silico Analiz ile Araştırılması

Amaç: Otofaji, hasarlı organellerin, hatalı katlanmış veya uzun ömürlü proteinlerin, ökaryotik hücrelerde lizozom aracılı uzaklaştırılmasından sorumlu olan majör bir hücresel yoldur ve mayadan memelilere kadar iyi düzeyde korunmuş fizyolojik mekanizmadır. Otofaji, hücre ölümü, hücre gelişimi, tümörün bastırılması ve ayrıca besin yoksunluğuna adaptasyon dahil birçok hücresel süreci düzenlemektedir. Otofaji, nörodejeneratif hastalıklar, bulaşıcı hastalıklar, metabolik hastalıklar ve kanserinde dahil olduğu çok çeşitli patolojilerle ilişkilendirilmiştir. Memeli otofajisi, 6 farklı protein kompleksi ile düzenlenmektedir. Bu kompleksler; ULK1 - ATG13 - FIP200 - ATG101, VPS34-VPS15- Beclin1, WIPI/ATG18 - ATG2 kompleksi, multi-spanning transmembran proteini ATG9A, ubikuitin benzeri ATG5/ ATG12 sistemi ve ubitin-benzeri ATG8/ LC3 sistemidir. Bu altı protein kompleksi, vezikül nükleazasyonu, otofagozomal membran uzaması ve integrasyonunda dahil olduğu otofagazom olgunlaşmasını düzenlemektedir. Son çalışmalar otofajinin prostat kanserindeki rolünü vurgulamaktadır. Bu nedenle, otofajinin bilinmeyen mekanizmalar ile gerçekleşen regülasyonu ve özellikle androjen aracılı gerçekleşen regülasyonu hakkındaki bilinmeyen süreçlerin anlaşılması önem taşımaktadır. Bu çalışmada otofaji ile ilişkili genlerin promotor bölgesinde in silico analizler ile varsayılan ARE’leri araştırmayı amaçladık. Materyal-Metot: Otofaji ile ilişkili hedef genlerin promotör dizileri UCSC ve EPD veri tabanından FASTA formatında ekstrakte edilerek, androjen resepötörü bağlanma motifi için varsayılan bağlanma bölgeleri V$GREF matrix’i kullanılarak matinspector biyoinformatik aracı ile analiz edildi. Bulgular: İn silico analiz sonuçlara göre otofaji ile ilişkili 33 farklı genin promotor bölgesinde varsayılan ARE’ler tanımlandı. Sonuç: Sonuçlarımız otofaji ile ilişkili komponentlerin androjen sinyalizasyonu ile sıkı şekilde düzenlenebileceğini önermektedir.

Investigation of Androgen Responsive Elements in Some Autophagy Related Genes via In Silico Analysis

Objective: Autophagy is a major cellular pathway that isresponsible for removal of damaged organelles, misfoldedor long-lived proteins by lysosome in eukaryotic cells, andit is a well conserved physiological mechanism from theyeast to mammalian. Autophagy is regulate many cellularprocess including cell death, cell development, tumorsuppression, and also adaptation to nutrient deprivation.Autophagy has been associated with several pathologies,including neurodegenerative diseases, infectious diseases,metabolic diseases and cancer. Mammalian autophagy isregulated by 6 different protein complexes. These complexesare the ULK1–ATG13–FIP200–ATG101, VPS34-VPS15-Beclin1, WIPI/ATG18–ATG2 complex, the multi-spanningtransmembrane protein ATG9A, the ubiquitin-like ATG5/ATG12 system, and the ubiquitin-like ATG8/LC3 conjugationsystem. These six-protein complex regulate differentsteps during autophagosome maturation, including vesiclenucleation, autophagosomal membrane elongation andintegration of autophagosome. Recent studies highlight therole of autophagy in prostate cancer. Thus, it is importantto understand the unknown processes about regulation ofautophagy with its different mechanisms, especially androgenmediated regulation. In this study, our aim was to investigatethe putative AREs in promoter sequence of autophagy relatedgenes by in silico analysis.Material-Method: Promoter sequences of the autophagyrelated target genes extracted from UCSC and EPD databasesin FASTA format and then analyzed putative binding sites forandrogen receptor binding motif (TGTTCTxxxAGAACA,AGAACAxxxAGAACA) by using V$GREF matrix frommatinspector bioinformatics tool.Results: The result of the in silico analysis indicates thatputative AREs in the promoter region of 33 different genesassociated with autophagy are identified.Conclusions: Our data the positive correlation between suggestthat autophagy related components may be tightly regulated byandrogen signaling.

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