TP53 stimulates and ZNF420 inhibits TP53AIP1 expression

Stable Identifier
R-HSA-6798611
Type
Reaction [omitted]
Species
Homo sapiens
Compartment
nucleoplasm, mitochondrial matrix
ReviewStatus
5/5
Locations in the PathwayBrowser
Expand all
General
SVG | 
PNG
Low
Medium
High
 | PPTX  | SBGN
TP53 stimulates and ZNF420 inhibits TP53AIP1 expression
Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout
TP53 (p53) bound to the p53 response element in the first intron of the TP53AIP1 (p53AIP1) gene stimulates transcription of TP53AIP1. TP53AIP1 protein product localizes to mitochondria and induces apoptosis through dissipation of the mitochondrial membrane potential via an unknown mechanism (Oda et al. 2000). In order to induce TP53AIP1 transcription, TP53 has to be phosphorylated at serine residue S46. DYRK2 kinase is activated by ATM in response to DNA damage and can phosphorylate TP53 at S46 upstream of TP53AIP1 induction (Taira et al. 2007).

The transcription factor ZNF420 (Apak) has a binding site in the first intron of TP53AIP1 that overlaps with the p53 response element. The binding of ZNF420 interferes with the binding of TP53 and results in the repression of TP53AIP1 transcription (Yuan et al. 2012).

Literature References
PubMed ID Title Journal Year
17349958 DYRK2 is targeted to the nucleus and controls p53 via Ser46 phosphorylation in the apoptotic response to DNA damage

Miki, Y, Nihira, K, Taira, N, Yoshida, K, Yamaguchi, T

Mol. Cell 2007
22334068 Apak competes with p53 for direct binding to intron 1 of p53AIP1 to regulate apoptosis

Tian, C, Wang, H, Song, S, Xing, G, Yin, Y, He, F, Li, D, Yuan, L, Zhang, L

EMBO Rep. 2012
11030628 p53AIP1, a potential mediator of p53-dependent apoptosis, and its regulation by Ser-46-phosphorylated p53

Oda, K, Tamai, K, Nishimori, H, Tanikawa, C, Mori, T, Arakawa, H, Matsuda, K, Nakamura, Y, Tokino, T, Taya, Y, Tanaka, T

Cell 2000
Participants
Input
Output
Participates
as an event of
This event is regulated
Negatively by
Regulator
ZNF420:TP53AIP1 Gene [nucleoplasm] (Homo sapiens)
Active Unit
ZNF420 [nucleoplasm]
Positively by
Regulator
p-S15,S20,S46-TP53 Tetramer:TP53AIP1 Gene [nucleoplasm] (Homo sapiens)
Active Unit
p-S15,S20,S46-TP53 Tetramer [nucleoplasm]
Authored
Orlic-Milacic, M  (2015-10-14)
Reviewed
Zaccara, S  (2016-02-04)
Inga, A  (2016-02-04)
Created
Orlic-Milacic, M  (2015-09-19)
Cite Us!