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

Abstract

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.

Keywords

• p53, p63, p73, cell cycle, gene family

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

Abstract

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.

Keywords

• p53, p63, p73, hücre döngüsü, gen ailesi

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