Search results for TP53I3

Showing 11 results out of 11

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Species

Types

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Protein (1 results from a total of 1)

Identifier: R-HSA-6799460
Species: Homo sapiens
Compartment: cytosol
Primary external reference: UniProt: TP53I3: Q53FA7

Interactor (1 results from a total of 1)

Identifier: EBI-1550792
Species: Homo sapiens
Primary external reference: IntAct: EBI-1550792

DNA Sequence (1 results from a total of 1)

Identifier: R-HSA-6799446
Species: Homo sapiens
Compartment: nucleoplasm
Primary external reference: ENSEMBL: ENSEMBL:ENSG00000115129

Reaction (4 results from a total of 4)

Identifier: R-HSA-6799466
Species: Homo sapiens
Compartment: cytosol
TP53I3 (PIG3) forms a homodimer. The dimer interface is formed by two beta strands and an alpha helix of the cofactor-binding domain. Beta strands of the two monomeric subunits are bonded through anti-parallel hydrogen bonds (Porte et al. 2009).
Identifier: R-HSA-6799722
Species: Homo sapiens
Compartment: cytosol
TP53I3 (PIG3) possesses a NADPH quinone reductase activity, with 1,2-naphthoquinone being its preferred substrate. TP53I3 reduces 1,2-naphthoquinone to a highly unstable semiquinone free radical. Semiquinone reacts with oxygen yielding a quinone and superoxide aninon. Reactive oxygen species (ROS) produced as a result of TP53I3 activity contribute to apoptosis (Porte et al. 2009).
Identifier: R-HSA-6799441
Species: Homo sapiens
Compartment: nucleoplasm
TP53 (p53) activates transcription of the TP53I3 (PIG3) gene by binding to the pentanucleotide microsatellite sequence in the TP53I3 gene promoter that shares a limited similarity with the consensus p53 response element (Contente et al. 2002). Transcription of the TP53I3 gene can also be activated by p53 family members TP63 (p63) and TP73 (p73) (Bergamaschi et al. 2004). ASPP proteins PPP1R13B (ASPP1) and TP53BP2 (ASPP2) form a complex with p53 family members, leading to increased binding of p53 family members to the TP53I3 promoter and enhanced transcription of TP53I3 (Samuels-Lev et al. 2001, Bergamaschi et al. 2004).
Identifier: R-HSA-6799462
Species: Homo sapiens
Compartment: nucleoplasm
TP53 (p53) binds a pentanucleotide microsatellite sequence in the promoter of the TP53I3 (PIG3) gene that shares a limited similarity with the consensus sequence of the p53 response element (Contente et al. 2002). TP63 (p63) and TP73 (p73), members of the p53 protein family, can also bind the promoter of TP53I3 (Bergamaschi et al. 2004). Formation of a complex between p53 family members and ASSP proteins PPP1R13B (ASPP1) or TP53BP2 (ASPP2) enhances binding of TP53 (Samuels-Lev et al. 2001), TP63 or TP73 to the TP53I3 promoter (Bergamaschi et al. 2004).

Complex (2 results from a total of 2)

Identifier: R-HSA-6799448
Species: Homo sapiens
Compartment: cytosol
Identifier: R-HSA-6799461
Species: Homo sapiens
Compartment: nucleoplasm

Pathway (2 results from a total of 2)

Identifier: R-HSA-6803205
Species: Homo sapiens
The exact mechanisms of action of several other pro-apoptotic TP53 (p53) targets, such as TP53I3 (PIG3), RABGGTA, BCL2L14, BCL6, NDRG1 and PERP, remain uncertain (Attardi et al. 2000, Guo et al. 2001, Samuels-Lev et al. 2001, Contente et al. 2002, Ihrie et al. 2003, Bergamaschi et al. 2004, Stein et al. 2004, Phan and Dalla-Favera 2004, Jen and Cheung 2005, Margalit et al. 2006, Zhang et al. 2007, Saito et al. 2009, Davies et al. 2009, Giam et al. 2012).
Identifier: R-HSA-5633008
Species: Homo sapiens
The tumor suppressor TP53 (p53) exerts its tumor suppressive role in part by regulating transcription of a number of genes involved in cell death, mainly apoptotic cell death. The majority of apoptotic genes that are transcriptional targets of TP53 promote apoptosis, but there are also several TP53 target genes that inhibit apoptosis, providing cells with an opportunity to attempt to repair the damage and/or recover from stress.
Pro-apoptotic transcriptional targets of TP53 involve TRAIL death receptors TNFRSF10A (DR4), TNFRSF10B (DR5), TNFRSF10C (DcR1) and TNFRSF10D (DcR2), as well as the FASL/CD95L death receptor FAS (CD95). TRAIL receptors and FAS induce pro-apoptotic signaling in response to external stimuli via extrinsic apoptosis pathway (Wu et al. 1997, Takimoto et al. 2000, Guan et al. 2001, Liu et al. 2004, Ruiz de Almodovar et al. 2004, Liu et al. 2005, Schilling et al. 2009, Wilson et al. 2013). IGFBP3 is a transcriptional target of TP53 that may serve as a ligand for a novel death receptor TMEM219 (Buckbinder et al. 1995, Ingermann et al. 2010).

TP53 regulates expression of a number of genes involved in the intrinsic apoptosis pathway, triggered by the cellular stress. Some of TP53 targets, such as BAX, BID, PMAIP1 (NOXA), BBC3 (PUMA) and probably BNIP3L, AIFM2, STEAP3, TRIAP1 and TP53AIP1, regulate the permeability of the mitochondrial membrane and/or cytochrome C release (Miyashita and Reed 1995, Oda et al. 2000, Samuels-Lev et al. 2001, Nakano and Vousden 2001, Sax et al. 2002, Passer et al. 2003, Bergamaschi et al. 2004, Li et al. 2004, Fei et al. 2004, Wu et al. 2004, Park and Nakamura 2005, Patel et al. 2008, Wang et al. 2012, Wilson et al. 2013). Other pro-apoptotic genes, either involved in the intrinsic apoptosis pathway, extrinsic apoptosis pathway or pyroptosis (inflammation-related cell death), which are transcriptionally regulated by TP53 are cytosolic caspase activators, such as APAF1, PIDD1, and NLRC4, and caspases themselves, such as CASP1, CASP6 and CASP10 (Lin et al. 2000, Robles et al. 2001, Gupta et al. 2001, MacLachlan and El-Deiry 2002, Rikhof et al. 2003, Sadasivam et al. 2005, Brough and Rothwell 2007).

It is uncertain how exactly some of the pro-apoptotic TP53 targets, such as TP53I3 (PIG3), RABGGTA, BCL2L14, BCL6, NDRG1 and PERP contribute to apoptosis (Attardi et al. 2000, Guo et al. 2001, Samuels-Lev et al. 2001, Contente et al. 2002, Ihrie et al. 2003, Bergamaschi et al. 2004, Stein et al. 2004, Phan and Dalla-Favera 2004, Jen and Cheung 2005, Margalit et al. 2006, Zhang et al. 2007, Saito et al. 2009, Davies et al. 2009, Giam et al. 2012).

TP53 is stabilized in response to cellular stress by phosphorylation on at least serine residues S15 and S20. Since TP53 stabilization precedes the activation of cell death genes, the TP53 tetramer phosphorylated at S15 and S20 is shown as a regulator of pro-apoptotic/pro-cell death genes. Some pro-apoptotic TP53 target genes, such as TP53AIP1, require additional phosphorylation of TP53 at serine residue S46 (Oda et al. 2000, Taira et al. 2007). Phosphorylation of TP53 at S46 is regulated by another TP53 pro-apoptotic target, TP53INP1 (Okamura et al. 2001, Tomasini et al. 2003). Additional post-translational modifications of TP53 may be involved in transcriptional regulation of genes presented in this pathway and this information will be included as evidence becomes available.

Activation of some pro-apoptotic TP53 targets, such as BAX, FAS, BBC3 (PUMA) and TP53I3 (PIG3) requires the presence of the complex of TP53 and an ASPP protein, either PPP1R13B (ASPP1) or TP53BP2 (ASPP2) (Samuels-Lev et al. 2001, Bergamaschi et al. 2004, Patel et al. 2008, Wilson et al. 2013), indicating how the interaction with specific co-factors modulates the cellular response/outcome.

TP53 family members TP63 and or TP73 can also activate some of the pro-apoptotic TP53 targets, such as FAS, BAX, BBC3 (PUMA), TP53I3 (PIG3), CASP1 and PERP (Bergamaschi et al. 2004, Jain et al. 2005, Ihrie et al. 2005, Patel et al. 2008, Schilling et al. 2009, Celardo et al. 2013).


For a review of the role of TP53 in apoptosis and pro-apoptotic transcriptional targets of TP53, please refer to Riley et al. 2008, Murray-Zmijewski et al. 2008, Bieging et al. 2014, Kruiswijk et al. 2015.

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