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tumor protein p73; p53-like transcription factor; p53-related protein (TP73, p73)

Function: - role in the apoptotic response to DNA damage - when overproduced, activates transcription from p53-responsive promoters & induces apoptosis - may be a tumor suppressor protein - functions in growth suppression - isoform beta interacts homotypically & with p53/TP53, whereas isoform alpha does not - isoform gamma interacts homotypically & with all p73 isoforms - isoform delta interacts with isoform gamma, isoform alpha, & homotypically - isoforms alpha & beta interact with HIPK2 - isoform alpha interacts with RANBP9 - found in a complex with pTP53 & CABLES1 - isoform beta interacts with WWOX - interacts with HECW2 - isoform alpha (but not isoform beta) is sumoylated on Lys-627, which potentiates proteasomal degradation but does not affect transcriptional activity - activated & stabilized by interaction with RANBP9 - not activated by UV radiation or actinomycin D (which cause DNA breaks) - induces p21WAF1 - when overexpressed can activate transcription of p53 responsive genes & induce apoptosis [2] - E2F1 induces p73. - activation of p73 is required for E2F1 induced apoptosis independent of p53 Cofactor: binds 1 Zn+2 per subunit (putative) Structure: - homologous to TP53 - 3 domains a) acidic transactivation domain b) central DNA binding domain c) C-terminal oligomerization domain that binds to the ABL tyrosine kinase SH3 domain - The WW-binding motif mediates interaction with WWOX - belongs to the p53 family Compartment: nucleus Alternative splicing: - named isoforms=9 - alpha & beta splice forms; beta form lacks exon 13 Expression: - expressed in brain, kidney, placenta, colon, heart, liver, spleen, skeletal muscle, prostate, thymus & pancreas - not induced by DNA damage Pathology: - maps to a chromosome region frequently mutated in diverse cell lines of human cancer - appears not to be frequently mutated in human cancers, in contrast to p53 - hemizygosity is observed in neuroblastoma & oligodendroglioma - site frequently deleted in neuroblastoma, melanoma, & ductal breast carcinoma - variants in TP73 correlate with risk for amyotrophic lateral sclerosis (ALS) & suggest a role for apoptosis in pathology of ALS [5]

Interactions

molecular events

Related

p73 gene

Specific

p73 alpha p73 beta

General

p53 family protein

Properties

SIZE: entity length = 636 aa MW = 70 kD COMPARTMENT: cell nucleus MOTIF: acidic region {1-55} MOTIF: acidic residue (SEVERAL) Transactivation {1-46} Tyr phosphorylation site {Y99} binding site SITE: 131-310 FOR-BINDING-OF: deoxyribonucleic acid (DNA) MOTIF: proline-rich region SITE: 168-171 MOTIF: proline residue (SEVERAL) Zn+2-binding site SITE: 194-194 Zn+2-binding site SITE: 197-197 Zn+2-binding site SITE: 258-258 Zn+2-binding site SITE: 262-262 nuclear translocation signal {287-304} HIPK2 interaction {345-380} mediates oligomerization {346-435} MOTIF: glutamine-rich region {391-394} MOTIF: glutamine residue (SEVERAL) WW-binding {483-487} MOTIF: proline-rich region SITE: 483-486 MOTIF: proline residue (SEVERAL)

Database Correlations

OMIM 601990 UniProt O15350 PFAM correlations Entrez Gene 7161 Kegg hsa:7161

References

  1. Kaghad M, Bonnet H, Yang A, Creancier L, Biscan JC, Valent A, Minty A, Chalon P, Lelias JM, Dumont X, Ferrara P, McKeon F, Caput D. Monoallelically expressed gene related to p53 at 1p36, a region frequently deleted in neuroblastoma and other human cancers. Cell. 1997 Aug 22;90(4):809-19. PMID: 9288759
  2. Jost CA, Marin MC, Kaelin WG Jr. p73 is a simian [correction of human] p53-related protein that can induce apoptosis. Nature. 1997 Sep 11;389(6647):191-4. Erratum in: Nature 1999 Jun 24;399(6738):817. PMID: 9296498
  3. Irwin M, Marin MC, Phillips AC, Seelan RS, Smith DI, Liu W, Flores ER, Tsai KY, Jacks T, Vousden KH, Kaelin WG Jr. Role for the p53 homologue p73 in E2F-1-induced apoptosis. Nature. 2000 Oct 5;407(6804):645-8. PMID: 11034215
  4. Entrez Gene :accession 7161
  5. George J Novel ALS Risk Gene Identified. Findings suggest apoptosis in motor neurons play an important role. MedPage Today June 17, 2021 https://www.medpagetoday.com/neurology/generalneurology/93170 - Russell KL et al Pathogenic effect of TP73 Gene Variants in People With Amyotrophic Lateral Sclerosis. Neurology 2021. June 16. PMID: 34135078 https://n.neurology.org/content/early/2021/06/15/WNL.0000000000012285

Component-of

molecular complex