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TP53 Regulates Transcription of Genes Involved in G2 Cell Cycle Arrest

Summary

Organism

Homo sapiens (human)

Reactome

R-HSA-6804114

PubChem

R-HSA-6804114

Description

TP53 contributes to the establishment of G2 arrest by inducing transcription of GADD45A and SFN, and by inhibiting transcription of CDC25C. TP53 induces GADD45A transcription in cooperation with chromatin modifying enzymes EP300, PRMT1 and CARM1 (An et al. 2004). GADD45A binds Aurora kinase A (AURKA), inhibiting its catalytic activity and preventing AURKA-mediated G2/M transition (Shao et al. 2006, Sanchez et al. 2010). GADD45A also forms a complex with PCNA. PCNA is involved in both normal and repair DNA synthesis. The effect of GADD45 interaction with PCNA, if any, on S phase progression, G2 arrest and DNA repair is not known (Smith et al. 1994, Hall et al. 1995, Sanchez et al. 2010, Kim et al. 2013). SFN (14-3-3-sigma) is induced by TP53 (Hermeking et al. 1997) and contributes to G2 arrest by binding to the complex of CDK1 and CCNB1 (cyclin B1) and preventing its translocation to the nucleus. Phosphorylation of a number of nuclear proteins by the complex of CDK1 and CCNB1 is needed for G2/M transition (Chan et al. 1999). While promoting G2 arrest, SFN can simultaneously inhibit apoptosis by binding to BAX and preventing its translocation to mitochondria, a step involved in cytochrome C release (Samuel et al. 2001). TP53 binds the promoter of the CDC25C gene in cooperation with the transcriptional repressor E2F4 and represses CDC25C transcription, thus maintaining G2 arrest (St Clair et al. 2004, Benson et al. 2014). The zinc finger transcription factor ZNF385A (HZF) is a direct transcriptional target of TP53 that can form a complex with TP53 and facilitate TP53-mediated induction of SFN transcription (Das et al. 2007).

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SPV: a JavaScript Signaling Pathway Visualizer, Bioinformatics, 2018

Displaying **all 9** entries
UniProt ID	Protein Name	Gene Symbol	Pathway Viewer
P04637	Cellular tumor antigen p53	P53 TP53	view
P12004	DNA sliding clamp PCNA	PCNA	view
P31947	14-3-3 protein sigma	HME1 SFN	view
Q07812	Apoptosis regulator BAX	BAX BCL2L4	view
Q08999	Retinoblastoma-like protein 2	RB2 RBL2	view
Q09472	Histone acetyltransferase p300	EP300 P300	view
Q16254	Transcription factor E2F4	E2F4	view
Q86X55	Histone-arginine methyltransferase CARM1	CARM1 PRMT4	view
Q99873	Protein arginine N-methyltransferase 1	HMT2 HRMT1L2 IR1B4 PRMT1	view

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