Recombinant Human p53 protein

特殊说明

形式

Liquid

附加说明

Purified by affinity chromatography

常规信息

功能

Multifunctional transcription factor that induces cell cycle arrest, DNA repair or apoptosis upon binding to its target DNA sequence (PubMed : 11025664, PubMed : 12524540, PubMed : 12810724, PubMed : 15186775, PubMed : 15340061, PubMed : 17317671, PubMed : 17349958, PubMed : 19556538, PubMed : 20673990, PubMed : 20959462, PubMed : 22726440, PubMed : 24051492, PubMed : 24652652, PubMed : 35618207, PubMed : 36634798, PubMed : 38653238, PubMed : 9840937). Acts as a tumor suppressor in many tumor types; induces growth arrest or apoptosis depending on the physiological circumstances and cell type (PubMed : 11025664, PubMed : 12524540, PubMed : 12810724, PubMed : 15186775, PubMed : 15340061, PubMed : 17189187, PubMed : 17317671, PubMed : 17349958, PubMed : 19556538, PubMed : 20673990, PubMed : 20959462, PubMed : 22726440, PubMed : 24051492, PubMed : 24652652, PubMed : 38653238, PubMed : 9840937). Negatively regulates cell division by controlling expression of a set of genes required for this process (PubMed : 11025664, PubMed : 12524540, PubMed : 12810724, PubMed : 15186775, PubMed : 15340061, PubMed : 17317671, PubMed : 17349958, PubMed : 19556538, PubMed : 20673990, PubMed : 20959462, PubMed : 22726440, PubMed : 24051492, PubMed : 24652652, PubMed : 9840937). One of the activated genes is an inhibitor of cyclin-dependent kinases. Apoptosis induction seems to be mediated either by stimulation of BAX and FAS antigen expression, or by repression of Bcl-2 expression (PubMed : 12524540, PubMed : 17189187). Its pro-apoptotic activity is activated via its interaction with PPP1R13B/ASPP1 or TP53BP2/ASPP2 (PubMed : 12524540). However, this activity is inhibited when the interaction with PPP1R13B/ASPP1 or TP53BP2/ASPP2 is displaced by PPP1R13L/iASPP (PubMed : 12524540). In cooperation with mitochondrial PPIF is involved in activating oxidative stress-induced necrosis; the function is largely independent of transcription. Induces the transcription of long intergenic non-coding RNA p21 (lincRNA-p21) and lincRNA-Mkln1. LincRNA-p21 participates in TP53-dependent transcriptional repression leading to apoptosis and seems to have an effect on cell-cycle regulation. Implicated in Notch signaling cross-over. Prevents CDK7 kinase activity when associated to CAK complex in response to DNA damage, thus stopping cell cycle progression. Isoform 2 enhances the transactivation activity of isoform 1 from some but not all TP53-inducible promoters. Isoform 4 suppresses transactivation activity and impairs growth suppression mediated by isoform 1. Isoform 7 inhibits isoform 1-mediated apoptosis. Regulates the circadian clock by repressing CLOCK-BMAL1-mediated transcriptional activation of PER2 (PubMed : 24051492).

序列相似性

Belongs to the p53 family.

翻译后修饰

Acetylation of Lys-382 by CREBBP enhances transcriptional activity (PubMed:10656795, PubMed:15448695, PubMed:20228809, PubMed:23431171). Acetylation of Lys-382 by EP300 (PubMed:10656795, PubMed:15448695, PubMed:20228809, PubMed:23431171). Deacetylation of Lys-382 by SIRT1 impairs its ability to induce proapoptotic program and modulate cell senescence (PubMed:10656795, PubMed:15448695, PubMed:20228809, PubMed:23431171). Deacetylation by SIRT2 impairs its ability to induce transcription activation in a AKT-dependent manner (PubMed:10656795, PubMed:15448695, PubMed:20228809, PubMed:23431171, PubMed:29681526). Acetylation at Lys-381 increases stability (PubMed:29474172). Deacetylation at Lys-381 by SIRT6 decreases its stability, thereby regulating cell senescence (PubMed:29474172). Acetylated at Lys-120 by KAT5, KAT6A and KAT8; regulating its ability to induce proapoptotic program (PubMed:17189187, PubMed:19854137, PubMed:23431171).. Lactylation by AARS1 prevents ability to undergo liquid-liquid phase separation (LLPS), thereby inhibiting transcription factor activity.. Phosphorylation on Ser residues mediates transcriptional activation. Phosphorylated by HIPK1 (By similarity). Phosphorylation at Ser-9 by HIPK4 increases repression activity on BIRC5 promoter. Phosphorylated on Thr-18 by VRK1, which may prevent the interaction with MDM2 (PubMed:10951572, PubMed:31527692). Phosphorylated on Ser-20 by CHEK2 in response to DNA damage, which prevents ubiquitination by MDM2. Phosphorylated on Ser-20 by PLK3 in response to reactive oxygen species (ROS), promoting p53/TP53-mediated apoptosis. Phosphorylated on Thr-55 by TAF1, which promotes MDM2-mediated degradation. Phosphorylated on Ser-33 by CDK7 in a CAK complex in response to DNA damage. Phosphorylated on Ser-46 by HIPK2 upon UV irradiation. Phosphorylation on Ser-46 is required for acetylation by CREBBP. Phosphorylated on Ser-392 following UV but not gamma irradiation. Phosphorylated by NUAK1 at Ser-15 and Ser-392; was initially thought to be mediated by STK11/LKB1 but it was later shown that it is indirect and that STK11/LKB1-dependent phosphorylation is probably mediated by downstream NUAK1 (PubMed:21317932). It is unclear whether AMP directly mediates phosphorylation at Ser-15. Phosphorylated on Thr-18 by isoform 1 and isoform 2 of VRK2. Phosphorylation on Thr-18 by isoform 2 of VRK2 results in a reduction in ubiquitination by MDM2 and an increase in acetylation by EP300. Stabilized by CDK5-mediated phosphorylation in response to genotoxic and oxidative stresses at Ser-15, Ser-33 and Ser-46, leading to accumulation of p53/TP53, particularly in the nucleus, thus inducing the transactivation of p53/TP53 target genes. Phosphorylated by DYRK2 at Ser-46 in response to genotoxic stress. Phosphorylated at Ser-315 and Ser-392 by CDK2 in response to DNA-damage. Phosphorylation at Ser-15 is required for interaction with DDX3X and gamma-tubulin (PubMed:28842590). Phosphorylation at Ser-392 regulates its ability to undergo liquid-liquid phase separation by increasing fluidity of TP53/p53 condensates (PubMed:35618207).. Dephosphorylated by PP2A-PPP2R5C holoenzyme at Thr-55. SV40 small T antigen inhibits the dephosphorylation by the AC form of PP2A.. May be O-glycosylated in the C-terminal basic region. Studied in EB-1 cell line.. Ubiquitinated by MDM2 and SYVN1, which leads to proteasomal degradation (PubMed:10722742, PubMed:12810724, PubMed:15340061, PubMed:17170702, PubMed:19880522, PubMed:29681526). Ubiquitinated by RFWD3, which works in cooperation with MDM2 and may catalyze the formation of short polyubiquitin chains on p53/TP53 that are not targeted to the proteasome (PubMed:10722742, PubMed:12810724, PubMed:20173098). Ubiquitinated by MKRN1 at Lys-291 and Lys-292, which leads to proteasomal degradation (PubMed:19536131). Deubiquitinated by USP10, leading to its stabilization (PubMed:20096447). Ubiquitinated by TRIM24, RFFL, RNF34 and RNF125, which leads to proteasomal degradation (PubMed:19556538). Ubiquitination by TOPORS induces degradation (PubMed:19473992). Deubiquitination by USP7, leading to stabilization (PubMed:15053880). Isoform 4 is monoubiquitinated in an MDM2-independent manner (PubMed:15340061). Ubiquitinated by COP1, which leads to proteasomal degradation (PubMed:19837670). Ubiquitination and subsequent proteasomal degradation is negatively regulated by CCAR2 (PubMed:25732823). Polyubiquitinated by C10orf90/FATS, polyubiquitination is 'Lys-48'-linkage independent and non-proteolytic, leading to TP53 stabilization (By similarity). Polyubiquitinated by MUL1 at Lys-24 which leads to proteasomal degradation (PubMed:21597459). Deubiquitinated by USP3, leading to stabilization (PubMed:28807825). Ubiquitinated by MSL2, promoting its cytoplasmic localization (PubMed:19033443).. Monomethylated at Lys-372 by SETD7, leading to stabilization and increased transcriptional activation (PubMed:15525938, PubMed:16415881). Monomethylated at Lys-370 by SMYD2, leading to decreased DNA-binding activity and subsequent transcriptional regulation activity (PubMed:17108971). Lys-372 monomethylation prevents interaction with SMYD2 and subsequent monomethylation at Lys-370 (PubMed:17108971). Dimethylated at Lys-373 by EHMT1 and EHMT2 (PubMed:20118233). Monomethylated at Lys-382 by KMT5A, promoting interaction with L3MBTL1 and leading to repress transcriptional activity (PubMed:17707234). Dimethylation at Lys-370 and Lys-382 diminishes p53 ubiquitination, through stabilizing association with the methyl reader PHF20 (PubMed:22864287). Demethylation of dimethylated Lys-370 by KDM1A prevents interaction with TP53BP1 and represses TP53-mediated transcriptional activation (PubMed:17805299). Monomethylated at Arg-333 and dimethylated at Arg-335 and Arg-337 by PRMT5; methylation is increased after DNA damage and might possibly affect TP53 target gene specificity (PubMed:19011621).. Sumoylated with SUMO1. Sumoylated at Lys-386 by UBC9.

亚细胞定位

Nucleus