NADİR KOÇAK, İBRAHİM HALİL YILDIRIM, Seval YILDIRIM CING

p53 ve p53 gen ailesi üyeleri olan p63 ve p73’ün hücresel işlevleri

p53, hücre akıbetinin belirlenmesinde önemli rol oynayan hücre döngüsünün durdurulması veya programlı hücre ölümüne yönlendirilmesi gibi hücresel birçok yolağın düzenlenmesinde görev alan bir transkripsiyon faktörüdür. p53 aracılığı ile programlı hücre ölümünün başlatılması veya hücre çoğalmasının durdurulması, hasarlı DNA replikasyonunu ve genetik olarak normal olmayan hücrelerin çoğalmasını engellemektedir. Bu nedenle p53 işlevlerinin mutasyon ya da delesyon ile engellenmesi hücre homeostasisin sağlanmasında da ayrıca önemlidir. Bununla birlikte, çalışmalar p53’ten yoksun farelerin ve Saos-2 gibi hücrelerin yaşamlarını devam ettirebildiklerini göstermektedir. Bu durum, p53’ten yoksun olan organizmalarda p53 işlevini karşılayan p53-ilişkili proteinlerin olabileceğini düşündürmüştür. p53 ilişkili p63 ve p73 proteinlerinin keşfi, p53’ten yoksun hücrelerde p53 bağımlı genlerin transkripsiyonlarına bir açıklama getirmiştir. p63 ve p73 proteinlerinin her ikisi de p53 proteini ile yüksek oranda benzerlik göstermekte ve p53’ün bazı işlevlerini de paylaşmaktadırlar. p53’ten farklı olarak p63 ve p73 insan kanserlerinde nadir olarak mutasyona uğramıştır. Burada p53 hakkındaki güncel bilgilerle beraber p53-ilişkili proteinler olan p63 ve p73 hakkındaki bilgileri de özetlemeye çalıştık.

Cellular functions of p53 and p53 gene family members p63 and p73

p53 is a transcription factor that regulates multiple cellular processes that are also important in cellular fates such as cell cycle arrest or programmed cell death. Induction of growth arrest or cell death by p53 prevents the replication of damaged DNA and proliferation of genetically abnormal cells. Therefore, inactivation of p53 by mutation or deletion is also important in ensuring the cellular homeostasis. However, studies showed that p53 deficient mice and cells such as Saos-2 cells are maintaining their life. This situation suggests that p53-related proteins might compensate the functions of p53 in p53 deficient organisms. The identification of two p53-related proteins, p63 and p73 revealed the transcription of p53 responsive genes in p53 deficient organisms. Both p63 and p73 proteins have high homology with the p53 protein and share some of the functions of p53. In contrast to p53, p63 and p73 rarely mutated in human cancers. Here we studied to summarize the current information about the p53 and other p53-related proteins, p63 and p73 that are included into the p53 gene family.

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