The p53 gene is a widely studied anti-oncogene, or tumor suppressor gene. The p53 gene product can act as a negative regulator of cell growth in response to DNA damage. Mutations and allelic loss of the p53 gene have been associated with malignant transformation in a wide variety of human tumors. p53 shares considerable sequence similarity with p73, a gene that maps to a region in chromosome 1 that is frequently deleted in neuroblastomas. However, p73 does not appear to be activated by DNA damaging agents. The p73 isoform p73α inhibits drug-induced apoptosis in small cell lung carcinoma cells, while the p73 isoform p73β promotes it. p73α also prevents Bax activation, mitochondrial dysfunction, caspase activation and is able to reduce apoptosis induced by the BH3-only protein PUMA (p53 upregulated modulator of apoptosis). There is an equilibrium between p73α and p73β, demonstrated by the fact that p73α inhibits the pro-apoptotic effect of p73β.
Background References
1. Venkatanarayan A et al. IAPP-driven metabolic reprogramming induces regression of p53-deficient tumours in vivo. Nature 517:626-30 (2015).
2. Zhang W et al. ELL inhibits E2F1 transcriptional activity by enhancing E2F1 deacetylation via recruitment of histone deacetylase 1. Mol Cell Biol 34:765-75 (2014).
Sequence Similarity
Belongs to the p53 family.
Tissue Specificity
Expressed in striatal neurons of patients with Huntington disease (at protein level). Brain, kidney, placenta, colon, heart, liver, spleen, skeletal muscle, prostate, thymus and pancreas. Highly expressed in fetal tissue.
Post-translational Modification
Isoform alpha (but not isoform beta) is sumoylated on Lys-627, which potentiates proteasomal degradation but does not affect transcriptional activity. Phosphorylation by PLK1 and PLK3 inhibits the transcription regulator activity and pro-apoptotic function.; Higher levels of phosphorylation seen in the brain from patients with Huntington disease.; Polyubiquitinated by RCHY1/PIRH2; leading to its degradation by the proteasome.
Western blot analysis of p73 on different lysates with Rabbit anti-p73 antibody (ET1609-80) at 1/1,000 dilution.
Lane 1: HAP1-parental cell lysate Lane 2: HAP1-p73 KD cell lysate
Lysates/proteins at 10 µg/Lane.
Predicted band size: 70 kDa Observed band size: 70 kDa
Exposure time: 3 minutes; ECL: K1802;
4-20% SDS-PAGE gel.
Proteins were transferred to a PVDF membrane and blocked with 5% NFDM/TBST for 1 hour at room temperature. The primary antibody (ET1609-80) at 1/1,000 dilution was used in 5% NFDM/TBST at 4℃ overnight. Goat Anti-Rabbit IgG - HRP Secondary Antibody (HA1001) at 1/50,000 dilution was used for 1 hour at room temperature.
Western blot analysis of p73 on 293 cell lysates. Proteins were transferred to a PVDF membrane and blocked with 5% BSA in PBS for 1 hour at room temperature. The primary antibody (ET1609-80, 1/500) was used in 5% BSA at room temperature for 2 hours. Goat Anti-Rabbit IgG - HRP Secondary Antibody (HA1001) at 1:5,000 dilution was used for 1 hour at room temperature.
ICC staining of p73 in MCF-7 cells (green). Formalin fixed cells were permeabilized with 0.1% Triton X-100 in TBS for 10 minutes at room temperature and blocked with 1% Blocker BSA for 15 minutes at room temperature. Cells were probed with the primary antibody (ET1609-80, 1/50) for 1 hour at room temperature, washed with PBS. Alexa Fluor®488 Goat anti-Rabbit IgG was used as the secondary antibody at 1/1,000 dilution. The nuclear counter stain is DAPI (blue).
Immunohistochemical analysis of paraffin-embedded human kidney tissue using anti-p73 antibody. The section was pre-treated using heat mediated antigen retrieval with Tris-EDTA buffer (pH 8.0-8.4) for 20 minutes.The tissues were blocked in 5% BSA for 30 minutes at room temperature, washed with ddH2O and PBS, and then probed with the primary antibody (ET1609-80, 1/50) for 30 minutes at room temperature. The detection was performed using an HRP conjugated compact polymer system. DAB was used as the chromogen. Tissues were counterstained with hematoxylin and mounted with DPX.
Immunohistochemical analysis of paraffin-embedded mouse skin tissue using anti-p73 antibody. The section was pre-treated using heat mediated antigen retrieval with Tris-EDTA buffer (pH 8.0-8.4) for 20 minutes.The tissues were blocked in 5% BSA for 30 minutes at room temperature, washed with ddH2O and PBS, and then probed with the primary antibody (ET1609-80, 1/50) for 30 minutes at room temperature. The detection was performed using an HRP conjugated compact polymer system. DAB was used as the chromogen. Tissues were counterstained with hematoxylin and mounted with DPX.
Immunohistochemical analysis of paraffin-embedded mouse kidney tissue using anti-p73 antibody. The section was pre-treated using heat mediated antigen retrieval with Tris-EDTA buffer (pH 8.0-8.4) for 20 minutes.The tissues were blocked in 5% BSA for 30 minutes at room temperature, washed with ddH2O and PBS, and then probed with the primary antibody (ET1609-80, 1/50) for 30 minutes at room temperature. The detection was performed using an HRP conjugated compact polymer system. DAB was used as the chromogen. Tissues were counterstained with hematoxylin and mounted with DPX.
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