Association of TP53 (p53) with various transcriptional co-fa...

created [InstanceEdit:6806333] Orlic-Milacic, Marija, 2015-10-22
dbId 6806332
displayName Association of TP53 (p53) with various transcriptional co-fa...
modified [InstanceEdit:8856568] Orlic-Milacic, Marija, 2016-02-10
schemaClass Summation
text Association of TP53 (p53) with various transcriptional co-factors can promote, inhibit or provide specificity towards either transcription of cell cycle arrest genes or transcription of cell death genes. Binding of the zinc finger protein ZNF385A (HZF), which is a transcriptional target of TP53, stimulates transcription of cell cycle arrest genes, such as CDKN1A (Das et al. 2007). Binding of POU4F1 (BRN3A) to TP53 also stimulates transcription of cell cycle arrest genes while inhibiting transcription of pro-apoptotic genes (Budhram-Mahadeo et al. 1999, Hudson et al. 2005).

Binding of ASPP family proteins PPP1R13B (ASPP1) or TP53BP2 (ASPP2) to TP53 stimulates transcription of pro-apoptotic TP53 targets (Samuels-Lev et al. 2001, Bergamaschi et al. 2004). Binding of the ASPP family member PPP1R13L (iASSP) inhibits TP53-mediated activation of pro-apoptotic genes probably by interfering with binding of stimulatory ASPPs to TP53 (Bergamaschi et al. 2003). Transcription of pro-apoptotic genes is also stimulated by binding of TP53 to POU4F2 (BRN3B) (Budrham-Mahadeo et al. 2006, Budhram-Mahadeo et al. 2014) or to hCAS/CSE1L (Tanaka et al. 2007).

Binding of co-factors to TP53 can also affect protein stability. For example, PHF20 binds to TP53 dimethylated on lysine residues K370 and K382 by unidentified protein lysine methyltransferase(s) and interferes with MDM2 binding, resulting in prolonged TP53 half-life (Cui et al. 2012). Long noncoding RNAs can contribute to p53-dependent transcriptional responses (Huarte et al. 2010). For a general review on this topic, see Espinosa 2008, Beckerman and Prives 2010, Murray-Zmijewski et al. 2008, An et al. 2004 and Barsotti and Prives 2010.

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