TP53 and PSME3

Number of citations of the paper that reports this interaction (PMID 18309296)
33

Data Source:
HPRD (in vitro)

		TP53	PSME3
Gene Name		tumor protein p53	proteasome (prosome, macropain) activator subunit 3 (PA28 gamma; Ki)
Image			No pdb structure
Gene Ontology Annotations	Cellular Component	Chromatin Nuclear Chromatin Nucleus Nucleoplasm Replication Fork Transcription Factor TFIID Complex Nucleolus Cytoplasm Mitochondrion Mitochondrial Matrix Endoplasmic Reticulum Cytosol Nuclear Matrix Nuclear Body PML Body Protein Complex	Proteasome Complex Nucleus Nucleoplasm Cytoplasm Cytosol Proteasome Activator Complex Membrane
	Molecular Function	RNA Polymerase II Core Promoter Sequence-specific DNA Binding Sequence-specific DNA Binding RNA Polymerase II Transcription Factor Activity Core Promoter Sequence-specific DNA Binding RNA Polymerase II Core Promoter Proximal Region Sequence-specific DNA Binding Transcription Factor Activity Involved In Positive Regulation Of Transcription RNA Polymerase II Transcription Factor Binding RNA Polymerase II Transcription Regulatory Region Sequence-specific DNA Binding Transcription Factor Activity Involved In Positive Regulation Of Transcription Protease Binding P53 Binding DNA Binding Chromatin Binding Damaged DNA Binding Sequence-specific DNA Binding Transcription Factor Activity Copper Ion Binding Protein Binding ATP Binding Transcription Factor Binding Zinc Ion Binding Enzyme Binding Protein Kinase Binding Protein Phosphatase Binding Receptor Tyrosine Kinase Binding Ubiquitin Protein Ligase Binding Histone Deacetylase Regulator Activity Histone Acetyltransferase Binding Identical Protein Binding Transcription Regulatory Region DNA Binding Protein Heterodimerization Activity Protein N-terminus Binding Chaperone Binding Protein Phosphatase 2A Binding MDM2/MDM4 Family Protein Binding	P53 Binding Protein Binding Endopeptidase Activator Activity MDM2/MDM4 Family Protein Binding
	Biological Process	Protein Import Into Nucleus, Translocation Negative Regulation Of Transcription From RNA Polymerase II Promoter DNA Strand Renaturation In Utero Embryonic Development Somitogenesis Release Of Cytochrome C From Mitochondria T Cell Proliferation Involved In Immune Response B Cell Lineage Commitment T Cell Lineage Commitment Response To Ischemia Base-excision Repair Nucleotide-excision Repair Double-strand Break Repair Regulation Of Transcription, DNA-templated Transcription From RNA Polymerase II Promoter Protein Complex Assembly Apoptotic Process Cellular Response To DNA Damage Stimulus DNA Damage Response, Signal Transduction By P53 Class Mediator Resulting In Cell Cycle Arrest DNA Damage Response, Signal Transduction By P53 Class Mediator Resulting In Transcription Of P21 Class Mediator ER Overload Response Cell Cycle Arrest Transforming Growth Factor Beta Receptor Signaling Pathway Notch Signaling Pathway Ras Protein Signal Transduction Multicellular Organismal Development Gastrulation Negative Regulation Of Neuroblast Proliferation Cell Aging Blood Coagulation Protein Localization Negative Regulation Of DNA Replication Cell Proliferation Negative Regulation Of Cell Proliferation Determination Of Adult Lifespan RRNA Transcription Response To Salt Stress Response To X-ray Response To Gamma Radiation Positive Regulation Of Cardiac Muscle Cell Apoptotic Process Viral Process Cerebellum Development Cell Differentiation Negative Regulation Of Cell Growth DNA Damage Response, Signal Transduction By P53 Class Mediator Negative Regulation Of Transforming Growth Factor Beta Receptor Signaling Pathway Positive Regulation Of Histone Deacetylation Chromatin Assembly Mitotic G1 DNA Damage Checkpoint Positive Regulation Of Protein Oligomerization T Cell Differentiation In Thymus Regulation Of Tissue Remodeling Cellular Protein Localization Cellular Response To UV Multicellular Organism Growth Cellular Response To Drug Positive Regulation Of Mitochondrial Membrane Permeability Cellular Response To Glucose Starvation Intrinsic Apoptotic Signaling Pathway In Response To DNA Damage By P53 Class Mediator Regulation Of Apoptotic Process Positive Regulation Of Apoptotic Process Negative Regulation Of Apoptotic Process Entrainment Of Circadian Clock By Photoperiod Mitochondrial DNA Repair Positive Regulation Of Neuron Apoptotic Process Negative Regulation Of Transcription, DNA-templated Positive Regulation Of Transcription, DNA-templated Positive Regulation Of Transcription From RNA Polymerase II Promoter Response To Antibiotic Regulation Of Mitochondrial Membrane Permeability Negative Regulation Of Fibroblast Proliferation Circadian Behavior Embryonic Organ Development Positive Regulation Of Peptidyl-tyrosine Phosphorylation Negative Regulation Of Helicase Activity Protein Tetramerization Neuron Apoptotic Process Positive Regulation Of Thymocyte Apoptotic Process Necroptotic Process Positive Regulation Of Cell Cycle Arrest Cellular Response To Hypoxia Cellular Response To Ionizing Radiation Mitotic Cell Cycle Arrest Intrinsic Apoptotic Signaling Pathway By P53 Class Mediator Positive Regulation Of Release Of Cytochrome C From Mitochondria Positive Regulation Of Cell Aging Replicative Senescence Oxidative Stress-induced Premature Senescence Intrinsic Apoptotic Signaling Pathway Oligodendrocyte Apoptotic Process Positive Regulation Of Protein Insertion Into Mitochondrial Membrane Involved In Apoptotic Signaling Pathway Negative Regulation Of Macromitophagy Regulation Of Mitochondrial Membrane Permeability Involved In Apoptotic Process Regulation Of Intrinsic Apoptotic Signaling Pathway By P53 Class Mediator Regulation Of Fibroblast Apoptotic Process Negative Regulation Of Reactive Oxygen Species Metabolic Process Positive Regulation Of Reactive Oxygen Species Metabolic Process Positive Regulation Of Intrinsic Apoptotic Signaling Pathway	G1/S Transition Of Mitotic Cell Cycle Protein Polyubiquitination Mitotic Cell Cycle Antigen Processing And Presentation Of Peptide Antigen Via MHC Class I Antigen Processing And Presentation Of Exogenous Peptide Antigen Via MHC Class I, TAP-dependent Regulation Of Cellular Amino Acid Metabolic Process Apoptotic Process DNA Damage Response, Signal Transduction By P53 Class Mediator Resulting In Cell Cycle Arrest Gene Expression Positive Regulation Of Endopeptidase Activity Viral Process Anaphase-promoting Complex-dependent Proteasomal Ubiquitin-dependent Protein Catabolic Process Cellular Nitrogen Compound Metabolic Process Antigen Processing And Presentation Of Exogenous Peptide Antigen Via MHC Class I Regulation Of Apoptotic Process Negative Regulation Of Apoptotic Process Small Molecule Metabolic Process Negative Regulation Of Ubiquitin-protein Ligase Activity Involved In Mitotic Cell Cycle Positive Regulation Of Ubiquitin-protein Ligase Activity Involved In Regulation Of Mitotic Cell Cycle Transition Regulation Of Ubiquitin-protein Ligase Activity Involved In Mitotic Cell Cycle Regulation Of Proteasomal Protein Catabolic Process Negative Regulation Of Canonical Wnt Signaling Pathway Positive Regulation Of Canonical Wnt Signaling Pathway Negative Regulation Of Extrinsic Apoptotic Signaling Pathway
Pathways		Cellular Senescence Activation of BH3-only proteins p53-Dependent G1/S DNA damage checkpoint Oncogene Induced Senescence p53-Dependent G1 DNA Damage Response Formation of Senescence-Associated Heterochromatin Foci (SAHF) Pre-NOTCH Transcription and Translation Stabilization of p53 Transcriptional activation of p53 responsive genes Programmed Cell Death Pre-NOTCH Expression and Processing G1/S DNA Damage Checkpoints Intrinsic Pathway for Apoptosis Transcriptional activation of cell cycle inhibitor p21 DNA Damage/Telomere Stress Induced Senescence Signaling by NOTCH Factors involved in megakaryocyte development and platelet production Activation of NOXA and translocation to mitochondria Oxidative Stress Induced Senescence Autodegradation of the E3 ubiquitin ligase COP1 Activation of PUMA and translocation to mitochondria Cell Cycle Checkpoints	Hedgehog 'off' state misspliced GSK3beta mutants stabilize beta-catenin Hh ligand biogenesis disease T41 mutants of beta-catenin aren't phosphorylated Downstream signaling events of B Cell Receptor (BCR) Degradation of beta-catenin by the destruction complex Stabilization of p53 S33 mutants of beta-catenin aren't phosphorylated AXIN mutants destabilize the destruction complex, activating WNT signaling Removal of licensing factors from origins Switching of origins to a post-replicative state Mitotic G1-G1/S phases Regulation of mRNA stability by proteins that bind AU-rich elements misspliced LRP5 mutants have enhanced beta-catenin-dependent signaling DNA Replication Pre-Initiation S45 mutants of beta-catenin aren't phosphorylated APC/C:Cdc20 mediated degradation of mitotic proteins Regulation of APC/C activators between G1/S and early anaphase SCF(Skp2)-mediated degradation of p27/p21 deletions in the AMER1 gene destabilize the destruction complex Autodegradation of the E3 ubiquitin ligase COP1 AMER1 mutants destabilize the destruction complex Activation of APC/C and APC/C:Cdc20 mediated degradation of mitotic proteins APC:Cdc20 mediated degradation of cell cycle proteins prior to satisfation of the cell cycle checkpoint PCP/CE pathway Adaptive Immune System CDK-mediated phosphorylation and removal of Cdc6 Hedgehog ligand biogenesis APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1 Separation of Sister Chromatids HIV Infection Ubiquitin-dependent degradation of Cyclin D APC truncation mutants have impaired AXIN binding Assembly of the pre-replicative complex Autodegradation of Cdh1 by Cdh1:APC/C p53-Dependent G1 DNA Damage Response S37 mutants of beta-catenin aren't phosphorylated XAV939 inhibits tankyrase, stabilizing AXIN p53-Independent DNA Damage Response p53-Independent G1/S DNA damage checkpoint G1/S DNA Damage Checkpoints Vpu mediated degradation of CD4 Synthesis of DNA M/G1 Transition Ubiquitin-dependent degradation of Cyclin D1 TCF dependent signaling in response to WNT SCF-beta-TrCP mediated degradation of Emi1 degradation of AXIN Signaling by Hedgehog Regulation of mitotic cell cycle Degradation of GLI1 by the proteasome degradation of DVL Cell Cycle Checkpoints Signaling by WNT in cancer GLI3 is processed to GLI3R by the proteasome Regulation of Apoptosis Degradation of GLI2 by the proteasome Signaling by the B Cell Receptor (BCR) Vif-mediated degradation of APOBEC3G Ubiquitin Mediated Degradation of Phosphorylated Cdc25A p53-Dependent G1/S DNA damage checkpoint truncated APC mutants destabilize the destruction complex TCF7L2 mutants don't bind CTBP Signaling by Wnt Cyclin E associated events during G1/S transition APC/C:Cdc20 mediated degradation of Securin AUF1 (hnRNP D0) destabilizes mRNA CDK-mediated phosphorylation and removal of Cdc6 RNF mutants show enhanced WNT signaling and proliferation G1/S Transition truncations of AMER1 destabilize the destruction complex Processing-defective Hh variants abrogate ligand secretion Host Interactions of HIV factors phosphorylation site mutants of CTNNB1 are not targeted to the proteasome by the destruction complex Regulation of activated PAK-2p34 by proteasome mediated degradation AXIN missense mutants destabilize the destruction complex S Phase APC/C-mediated degradation of cell cycle proteins Cyclin A:Cdk2-associated events at S phase entry SCF(Skp2)-mediated degradation of p27/p21 Mitotic Metaphase and Anaphase Regulation of ornithine decarboxylase (ODC) Antigen processing: Ubiquitination & Proteasome degradation Orc1 removal from chromatin Mitotic Anaphase M Phase APC truncation mutants are not K63 polyubiquitinated Metabolism of amino acids and derivatives Hedgehog 'on' state Programmed Cell Death Class I MHC mediated antigen processing & presentation Regulation of DNA replication Cell Cycle, Mitotic beta-catenin independent WNT signaling Orc1 removal from chromatin Activation of NF-kappaB in B cells Asymmetric localization of PCP proteins deletions in the AXIN genes in hepatocellular carcinoma result in elevated WNT signaling Cross-presentation of soluble exogenous antigens (endosomes) Antigen processing-Cross presentation CDT1 association with the CDC6:ORC:origin complex ER-Phagosome pathway
Drugs
Diseases
GWAS
Protein-Protein Interactions		387 interactors: ABL1 ACTA1 AGT AIMP2 ANK2 ANKRD2 ANXA2 ANXA3 ANXA7 APEX1 APOH APTX ARID1A ARID3A ARIH2 ARL3 ASH2L ATF3 ATM ATR AURKA BACH1 BAIAP2L1 BAK1 BANP BARD1 BCL2 BCL2L1 BCL2L2 BCR BLM BMP1 BRCA1 BRCA2 BRF1 BTBD2 BTK C10orf90 CABLES1 CABLES2 CAPG CAPN1 CARM1 CCDC106 CCL18 CCNA2 CCNG1 CCNH CCT5 CD40LG CDC14A CDC14B CDC25C CDC42 CDK1 CDK2 CDK5 CDK7 CDK8 CDK9 CDKN2C CEBPZ CHD3 CHEK1 CHEK2 CHUK COPS2 COPS3 COPS4 COPS5 COPS6 COPS7A COPS8 COX17 CR2 CREBBP CSNK1A1 CSNK1D CSNK2A1 CSNK2B CUL9 CXXC1 DAPK3 DAXX DDB1 DDX5 DHCR24 DHFR DLEU1 DNAJC7 DVL2 E2F1 E4F1 EEF2 EFEMP2 EGR1 EHMT1 EHMT2 EIF2AK2 EIF2S2 ELL EP300 EPHA3 ERCC2 ERCC3 ERCC6 ERH ESR1 FAM173A FBXO11 FBXO42 FCAMR FXYD6 FZR1 GADD45A GNL3 GPS1 GPS2 GPX2 GSK3B GSTM4 GTF2H1 GTF2H4 HABP4 HDAC1 HDAC2 HDAC3 HECTD3 HECW1 HERC2 HIF1A HIPK1 HIPK2 HMGB1 HMGB2 HNF4A HNRNPUL1 HSP90AA1 HSP90AB1 HSPA1A HSPA9 HSPB1 HTT HUWE1 IFI16 IKBKB ING1 ING4 ING5 IRF7 ITPK1 KANSL1 KAT2B KAT5 KAT6A KAT7 KAT8 KDM1A KDM4D KIAA0087 KLF4 KLF6 KPNA2 KPNA4 KPNB1 LAMA4 MAD2L1BP MAGEA2 MAGEB18 MAPK1 MAPK10 MAPK14 MAPK3 MAPK8 MAPK9 MAPKAPK5 MCL1 MDC1 MDH1 MDM2 MDM4 MED1 MED17 MED21 MEN1 MIF MNAT1 MNDA MPHOSPH6 MSL2 MSX1 MTA1 MTA2 MUC1 MUL1 MVP MYBBP1A NABP2 NAP1L1 NCL NCOA1 NCOA2 NCOA3 NDN NEDD8 NFKBIA NFYA NFYB NMT1 NMT2 NPM1 NQO1 NR0B2 NR3C1 NR4A1 OTUD5 PAFAH1B3 PARP1 PATZ1 PBK PCDHA4 PDLIM7 PER2 PHB PIAS1 PIAS2 PIAS4 PIN1 PLAGL1 PLK1 PLK3 PML PNP POLA1 PPA1 PPARGC1A PPM1D PPP1CA PPP1CC PPP1R13L PPP2CA PPP2R2B PPP4C PRIM1 PRKCA PRKD1 PRKDC PRKRA PRKRIR PRMT1 PSMB3 PSMC5 PSMD11 PSME3 PTEN PTGS2 PTK2 PTTG1 RAB4A RAD51 RANBP2 RANBP9 RAP1B RBBP5 RCC1 RCHY1 RFWD2 RNF128 RNF38 RPA1 RPS3 RRM2 RRM2B S100A2 S100A4 S100A6 S100A8 S100B SAT1 SCAMP1 SERPINB9 SET SETD1A SETD7 SETD8 SFN SHISA5 SIN3A SIN3B SIRT1 SMAD2 SMAD3 SMARCA4 SMARCB1 SMARCD1 SMN1 SMYD2 SNRPN SP1 SP3 SQSTM1 SRSF1 SSTR3 STAT6 STK11 STK4 STRA13 STX5 SULT1E1 SUMO1 SYVN1 TADA3 TAF1 TAF1A TAF1B TAF1C TAF9 TAF9B TBP TDG TEC TEP1 TFAP2A TFAP2C TFDP1 THAP8 THRB TK1 TOP1 TOP2A TOP2B TOPORS TP53BP1 TP53BP2 TP53INP1 TP53RK TP63 TP73 TRIAP1 TRIM27 TRIM39 TSC22D1 TSC22D3 TSG101 TTK TXN UBB UBE2A UBE2D1 UBE2I UBE2J1 UBE2K UBE2M UBE2N UBE3A UBE4B UBR5 UFD1L UHRF2 UIMC1 USP10 USP42 USP7 UTP14A VPRBP VRK1 WDR33 WDR5 WDR82 WRN WT1 WWOX XAF1 XRCC6 YBX1 YWHAG YWHAZ YY1 ZBTB2 ZBTB7A ZCCHC10 ZHX1 ZMIZ2 ZNF148 ZNF24 ZNF302 ZNHIT1	35 interactors: ADAP1 AICDA ATN1 ATP5B BBS2 CASP3 CASP6 CASP7 COIL CREBBP DIP2A DTNBP1 EAF1 FBXO7 FXR2 HSPA5 ITPKB KANSL1 MDM2 NCOA3 NUDT18 PFDN5 PRKAB2 PRR13 SERF2 SIRT1 SMURF1 SPG7 TBXA2R TNFAIP8L1 TP53 TXN2 WDR25 YWHAQ ZCCHC10
Entrez ID		7157	10197
HPRD ID		01859	05500
Ensembl ID		ENSG00000141510	ENSG00000131467
Uniprot IDs		H2EHT1 K7PPA8 P04637 Q53GA5	P61289 Q6MZZ1
PDB IDs		1A1U 1AIE 1C26 1DT7 1GZH 1H26 1HS5 1JSP 1KZY 1MA3 1OLG 1OLH 1PES 1PET 1SAE 1SAF 1SAK 1SAL 1TSR 1TUP 1UOL 1XQH 1YC5 1YCQ 1YCR 1YCS 2AC0 2ADY 2AHI 2ATA 2B3G 2BIM 2BIN 2BIO 2BIP 2BIQ 2F1X 2FEJ 2FOJ 2FOO 2GS0 2H1L 2H2D 2H2F 2H4F 2H4H 2H4J 2H59 2J0Z 2J10 2J11 2J1W 2J1X 2J1Y 2J1Z 2J20 2J21 2K8F 2L14 2LY4 2OCJ 2PCX 2VUK 2WGX 2X0U 2X0V 2X0W 2XWR 2YBG 2YDR 2Z5S 2Z5T 3D05 3D06 3D07 3D08 3D09 3D0A 3DAB 3DAC 3IGK 3IGL 3KMD 3KZ8 3LW1 3OQ5 3PDH 3Q01 3Q05 3Q06 3SAK 3TG5 3TS8 3ZME 4AGL 4AGM 4AGN 4AGO 4AGP 4AGQ 4BUZ 4BV2 4HFZ 4HJE 4IBQ 4IBS 4IBT 4IBU 4IBV 4IBW 4IBY 4IBZ 4IJT 4KVP 4LO9 4LOE 4LOF
Enriched GO Terms of Interacting Partners?		Cellular Response To Stress Positive Regulation Of Cellular Metabolic Process Regulation Of Metabolic Process Cellular Response To DNA Damage Stimulus Positive Regulation Of Metabolic Process Regulation Of Gene Expression Nucleobase-containing Compound Metabolic Process Regulation Of Nitrogen Compound Metabolic Process Cellular Nitrogen Compound Metabolic Process Cellular Aromatic Compound Metabolic Process Response To Stress Heterocycle Metabolic Process Positive Regulation Of Gene Expression Regulation Of Transcription, DNA-templated Negative Regulation Of Cellular Metabolic Process Cellular Metabolic Process Regulation Of Nucleic Acid-templated Transcription Regulation Of RNA Biosynthetic Process Regulation Of RNA Metabolic Process Positive Regulation Of Cellular Biosynthetic Process Positive Regulation Of Transcription, DNA-templated Cell Cycle Positive Regulation Of Macromolecule Biosynthetic Process Nitrogen Compound Metabolic Process Cellular Protein Modification Process Regulation Of Transcription From RNA Polymerase II Promoter RNA Biosynthetic Process Transcription, DNA-templated Regulation Of Apoptotic Process Regulation Of Cell Death Regulation Of Cellular Process Regulation Of Cellular Protein Metabolic Process Regulation Of Protein Metabolic Process Cellular Response To Stimulus Chromosome Organization Regulation Of Cell Cycle Cellular Macromolecule Biosynthetic Process Cell Cycle Process Macromolecule Biosynthetic Process Negative Regulation Of Gene Expression Cellular Protein Metabolic Process Response To Stimulus RNA Metabolic Process Negative Regulation Of Biosynthetic Process Chromatin Modification Gene Expression Chromatin Organization Apoptotic Process Programmed Cell Death Negative Regulation Of Nucleic Acid-templated Transcription	Response To Nutrient Levels Response To Extracellular Stimulus Negative Regulation Of Transforming Growth Factor Beta Receptor Signaling Pathway Regulation Of Metabolic Process Cellular Response To Nutrient Levels Intrinsic Apoptotic Signaling Pathway Negative Regulation Of Gene Expression Negative Regulation Of Helicase Activity Cellular Response To Extracellular Stimulus Cellular Response To Hypoxia Cellular Response To Decreased Oxygen Levels Regulation Of Transforming Growth Factor Beta Receptor Signaling Pathway Mitochondrion Organization Negative Regulation Of Transmembrane Receptor Protein Serine/threonine Kinase Signaling Pathway Negative Regulation Of Cellular Response To Growth Factor Stimulus Cellular Response To Oxygen Levels Peptidyl-lysine Acetylation Peptidyl-lysine Modification Positive Regulation Of Cell Aging Regulation Of Signal Transduction By P53 Class Mediator Regulation Of Signal Transduction Apoptotic Process Protein Acetylation Glial Cell Apoptotic Process Programmed Cell Death Regulation Of Gene Expression Anatomical Structure Development Response To Hypoxia Developmental Process Cell Death Death Mitochondrial Transport Response To Organic Substance Regulation Of Cellular Process Neuron Apoptotic Process Response To Antibiotic Regulation Of Signaling Cellular Component Disassembly Involved In Execution Phase Of Apoptosis ER Overload Response Apoptotic Signaling Pathway Neuron Death Regulation Of Cellular Response To Growth Factor Stimulus Cellular Response To Organic Substance Intracellular Transport Proteolysis Multicellular Organismal Development Negative Regulation Of DNA Damage Response, Signal Transduction By P53 Class Mediator Activation Of Cysteine-type Endopeptidase Activity Involved In Apoptotic Process By Cytochrome C Execution Phase Of Apoptosis Cellular Response To Oxidative Stress
Tagcloud ?		anchor anchorage artificial assign bac backcross bacs bands bovine bta19 centromere chrnb1 chromosomes colour construct cryb1 fish gh1 hybrid interspecies library linkage locations loci map meiotic nf1 p4hb unresolved	11sgamma amplification balance basal bioinformatics biotinylated called cdna ends export feedback immunoprecipitation ligase loop luciferase maintains negatively p53 pa28gamma precipitation promoter promotes promoting race reggamma regulates rlm start utilizing
Tagcloud (Difference) ?		anchor anchorage artificial assign bac backcross bacs bands bovine bta19 centromere chrnb1 chromosomes colour construct cryb1 fish gh1 hybrid interspecies library linkage locations loci map meiotic nf1 p4hb unresolved	11sgamma amplification balance basal bioinformatics biotinylated called cdna ends export feedback immunoprecipitation ligase loop luciferase maintains negatively p53 pa28gamma precipitation promoter promotes promoting race reggamma regulates rlm start utilizing
Tagcloud (Intersection) ?