The Role of Ubiquitine Proteasome Pathway in Carcinogenesis

Yıl 2010, Cilt: 19 Sayı: 1, 36 - 55, 01.03.2010

N.ceren Sümer Turanlıgil Yiğit Uyanıkgil

Öz

Ubiquitin works as a marker protein which targets misfolded or injured proteins to cellular degradation. It brings the abnormal proteins to a subcellular organelle named proteasome and it maintains the degradation of proteins in limited lenghts of peptides by leaving the process withuout being changed. Mistakes in ubiquitin-dependent proteolysis in various steps of carcinogenesis is known. In this review, we dealed with the effects of ubiquitin-proteasome pathway (UPP) on carcinogenesis via intercellular signaling molecules like Ras, transcription factors like NF-kB, cytokines like TNF-alfa Tumor necrosis factor), protooncogenes like p53 and MDM2(murine double minute 2), components of cell cycle and DNA repair proteins like BRCA1. We also focused on the relationship of UPP on antigen presentation which is active in immune response and its place in the aetiology of colon cancer to provide a specific example.

Anahtar Kelimeler

Ubiquitine, proteasome inhibitors, carcinogenesis, cell cycle, immune response

Ubikitin-Proteozom Yolağının Karsinojenezdeki Rolü

Öz

Ubikitin, yanlış katlanmş veya hasarlı proteinleri hücresel yıkıma götüren işaretleyici bir proteindir. Anormal proteinleri proteozom adlı subselüler bir organele götürür ve belirli uzunlukta peptidler halinde parçalanmalarını sağlayarak tepkimeden sağlam olarak ayrılır. Karsinojenezin çeşitli basamaklarında ubikitin aracılı proteolizde hasarlar rapor edilmiştir. Bu derlemede ubikitin-proteozom yolağının (UPY), Ras gibi hücre içi sinyalleme molekülleri, EGF (Epidermal Büyüme faktörü) gibi büyüme faktörleri, GH (Büyüme hormonu) gibi hormonlar, NF-kB (Nükleer faktör kappa B) gibi transkripsiyon faktörleri, TNF-alfa (transforme edici büyüme faktörü beta)gibi sitokinler, p53 ve MDM2 (murine double minute 2) gibi protoonkogenler, hücre siklusunun bileşenleri ve BRCA1 gibi DNA tamir proteinleri aracılığıyla kanserleşmeye katkısına değinilmektedir. Bunların yanı sıra bağışıklık sisteminin etkin olduğu antijen sunumuyla ilişkisine ve spesifik bir örnek olduğu için kolon kanseri etiyolojisindeki yeri vurgulanmaktadır. Anahtar kelimeler:

Anahtar Kelimeler

Ubikitin, proteozom inhibitörleri, karsinojenez, hücre siklusu, bağışık yanıt

Kaynakça

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