AURORA KİNAZLARIN KANSER VE HÜCRESEL SÜREÇLERDEKİ ROLÜ

Öz

Aurora kinazlar, Aurora A, B ve C şeklinde tanımlanan üç üyeye sahip, hücre döngüsünün düzenlenmesinde kritik rolleri olan yüksek oranda korunmuş serin/treonin kinaz ailesine ait proteinlerdir. Aurora kinazlar, kromozom stabilitesinin korunmasında önemli rolleri olan mitotik düzenleyiciler olarak hizmet etmektedir. Mitozdaki çeşitli olaylarda kritik roller üstlenen Aurora kinazlar, kromozomal ve sitoskeletal olayların koordinasyonu, iğ ipliği oluşumu kontrolü ve sitokinez gibi olaylarda görev alarak hücre döngüsünün sorunsuz ilerlemesini sağlamaktadır. Mitotik fonksiyonlarının yanı sıra, Aurora kinazlar mayoz bölünmenin düzenlenmesi süreçlerinde de yer almaktadırlar. Aurora kinazların gen amplifikasyonu/mutasyonu ve aşırı ifadesi çeşitli solid ve hematolojik kanserlerde tespit edilmiştir. Aurora kinazlar mitotik rolleri ile ilişkilendirilen onkojenik fonksiyonları ile kanser hücrelerinin çoğalması ve hayatta kalmalarını sağlamaktadırlar. Aurora kinaz aktivitesinin bozulması, sentrozom fonksiyonunda, iğ ipliklerinin oluşumunda, kromozomal hizalanmada ve sitokinezde sorunlara neden olarak mitotik anormallikler ve genetik istikrarsızlığa yol açmaktadır. Bu bulgular, Aurora kinazların kanserdeki önemli fonksiyonlarını vurgulayarak kanser terapötikleri için değerli hedefler olarak tanınmalarını sağlamaktadır. Bu derleme, Aurora kinazların yapı ve fonksiyonlarına genel bir bakış sunarak, bu kinazların kanserdeki onkojenik rollerini aydınlatmaktadır.

Anahtar Kelimeler

• Aurora kinazlar
• serin/treonin kinazlar
• kanser
• hücre döngüsü düzenleyicileri
• onkogenler

Aurora Kinases: Their Role in Cancer and Cellular Processes

Abstract

Aurora kinases, belonging to a highly conserved family of serine/threonine kinases with critical roles in the regulation of the cell cycle, comprise three members: Aurora kinase A, B, and C, which serve as key mitotic regulators essential for maintaining chromosome stability. Aurora kinases play crucial roles in multiple events in mitotic such as the coordination of chromosomal and cytoskeletal events, regulation of the spindle assembly checkpoint pathway and cytokinesis to ensure the smooth progression of the cell cycle. Besides their mitotic functions, Aurora kinases are also involved in the regulation of meiosis. Gene amplification/mutation and overexpression of Aurora kinases have been detected in various solid and haematological cancers. In human tumours, Aurora kinases exhibit oncogenic roles associated with their mitotic roles, which drive the cancer cell proliferation and survival. Deregulation of Aurora kinase activity causes failure in centrosome function, spindle assembly, chromosomal alignment, and cytokinesis, eventually resulting in the mitotic abnormalities and genetic instability. These findings emphasize the crucial functions of Aurora kinases in cancer, prompting their recognition as valuable targets for cancer therapy. This review provides an overview of the structures and functions of Aurora kinases and sheds light on their oncogenic roles in cancer.

Keywords

• Aurora kinases
• serine/threonine kinases
• cancer
• cell cycle regulators
• oncogenes

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