Background
p73 was identified as a long-lost cousin of tumor suppressor protein, p53 (4). p73 has high homology with p53 as well as with p63, a gene implicated in the maintenance of epithelial stem cells. Significant homology between p53, p63, and p73 (approximately 63% amino acid identity in the DNA-binding domain suggest that they may have overlapping functions in the regulation of gene expression (3). The targeted disruption of p73 gene leads to defects hippocampal dysgenesis, hydrocephalus, chronic inflammation and infections (2). Recently, spilicing variant mRNAs of p73 has been identified in MCF-7, a breast carcinoma cell line. These mRNAs code for variant p73 proteins bearing distinct carboxy-terminal structures suggesting that the carboxy-terminal region of p73 may be important for the functions of this protein (1). Tumor BioMarker: Vella et al (2003) found p73 to be upregulated in a significant fraction of anaplastic thyroid cancers, whereas it was not detectable in normal thyroid epithelial cells nor in papillary or follicular thyroid cancer.

Antigen
This antibody was raised against full-length human p73. It reacts with an epitope that is located on the N-terminal region of human p73. It does not cross react with p53.

Application Notes
1. IMG-246 recognizes all of the TAp73 isoforms (isoforms with the intact NH2-terminal transactivation domain) (Thottassery et el, 2006). 2. The IMG-246 5B429 clone has also been referred to as 429 in the literature. 3. Endogenous expression of p73 has been detected in a variety of cell types; for example, please refer to Sayan et al (2005), Vella et al (2003) and as well as other product citations for details regarding culture and treatment conditions. 4. Immunofluorescence microscopy fixation details can be found in Vella et al (2003). 5. Immunoprecipitation details can be found in Sayan et al (2005). 6. Imgenex offers several p73 antibodies with different features, many of which have been documented through publications.  For example, Sayan et al (2005) showed that p73 IMG-246 reacted with all tested TAp73 isoforms but not deltaNp73 whereas p73 IMG-259 showed reactivity against all p73 isoforms including delta Np73.  7. Caspase-cleaved p73 fragments, including 55 kDa and 45 kDa, have been described (Sayan et al, 2008). The ability of a given antibody to recognize a p73 fragment will depend on whether or not the antibody epitope is contained in the fragment. As p73 research continues to evolve, researchers are encouraged to refer to the published literature using the p73 antibodies to gain additional information.

Genebank Info (Protein)
NP_005418

Related Products

Reference
1. Kaghad M, Bonnet H, Yang A, Creancier L, Biscan JC., et al. Cell 90: 809-819 (1997).
2. Levrero M, De Laurenzi V, Costanz0 A, Gong J, Wang JY, and Melino G. J Cell Sci 113 (pt 10): 1661-1670 (2000).
3. Yang A, Walker N, Bronson R, Kaghad M, Oosterwegel M, et al. Nature 404: 99-103 (2000).
4. Ueda Y, Hijikata M, Takagi S, Chiba T, and Shimotohno K. Oncogene 18: 4993-4998 (1999).
5. Sayan AE, BS Sayan, V Gogvadze, D Dinsdale, U Nyman, TM Hansen, B Zhivotovsky, GM Cohen, RA Knight, G Melino. p73 and caspase-cleaved p73 fragments localize to mitochondria and augment TRAIL-induced apoptosis. Oncogene 27:4363-4372 (2008). 

Product Citations
1. Interaction of mismatch repair protein PMS2 and the p53-related transcription factor p73 in apoptosis response to cisplatin. Shimodaira H,  A Yoshioka-Yamashita, RD Kolodner, JYJ. Wang. PNAS, 100: 2420-2425 (2003). (Western blot)
2. Exclusion of c-Abl from the nucleus restrains the p73 tumor suppression function. Vella V,  J Zhu, F Frasca, C-Y Li, P Vigneri, R Vigneri, JYJ Wang. JBC, 278:25151-25157 (2003). (Western blot).
3. New antibodies recognizing p73: Comparison with commercial antibodies. Sayan AE, A Paradisi, B Vojtesek, RA Knight, G Melino, E Candi. Biochemical Biophysical Res Communications. 330:186-193. (2005). IMGENEX antibodies cited (p73 transfected cells, SK-N-SH human neuroblastoma cells, HaCaT human keratinocyte cells):
1. p73 (IMG-246): IP, Fig 3B (p73 transfected cells); WB, Figs 1 and 2 (p73 transfected cells).
2. p73 (IMG-259A): WB, Figs 1 and 2 (p73 transfected cells)
3. p73 (IMG-313A): WB, Figs 1, 2 and 3 (p73 transfected cells)

Note: See Table 1 for a summary of antibody results (WB and IF/ICC) in p73 transfected cells, SK-N-SH cells and HaCaT cells) IMG-313A (Clone 38C674.2) is referred to as OP181 in this publication.
4. MDM2 Is Required for Suppression of Apoptosis by Activated Akt1 in Salivary Acinar Cells. Kirsten H. Limesand, Kathryn L. Schwertfeger, and Steven M. Anderson. Mol. Cell. Biol., 26: 8840-8856 (2006).
5. Ser46 phosphorylation of p53 is not always sufficient to induce apoptosis: multiple mechanisms of regulation of p53-dependent apoptosis. Kurihara A, H Nagoshi, M Yabuki, R Okuyama, M Obinata, and S Ikawa. Genes Cells 12: 853-861 (2007).  WB: U20S cells (Fig 5B) and HCT116-53-/- cells (Fig 5G). The p73 IMG-246 antibody was also siRNA validated (Fig 5B) and p73 adenovirus infected validated (Fig 5G) in this citation.

6. Ubiquitin-dependent degradation of p73 is inhibited by PML. Bernassola F, P Salomoni, A Oberst, CJ Di Como, M Pagano, G Melino, and PP Pandolfi. J Exp Med 199:1545-1557. WB: HCT-116 human colon carcinoma cells (Fig 1B) and mouse embryo fibroblasts (Fig 2B).
7. p73 tumor-suppressor activity is impaired in human thyroid cancers. Frasca F, V Vella, A Aloisi, A Mandarino, E Mazzon, R Vigneri, and P Vigneri. Cancer Res 63:5829-5837 (2003). WB: human thyroid cancer cell lines (Fig 1B - top blot and  Fig 6B); IF/ICC: human thyroid cancer cell lines (Figs 1C and 7C).
8. c-Abl-independent p73 stabilization during gemcitabine-or 4'-thio-Beta-D-arabinofuranosylcytosine-induced apoptosis in wild-type and p53-null colorecetal cancer cells. Thottassery JV, L Westbrook, H Someya, and WB Parker. Mol Cancer Ther 5:400-410 (2006). Imgenex antbodies cited: p73 (IMG-246 and IMG-259A) for WB (Figs 5A, 6, 7 and 8B) in HCT 116 human colorectal cell lines (wild-type and p53 knockouts).   
9. Family members p53 and p73 act together in chromatin modification and direct repression of a-fetoprotein transcription. Cui R, TT Nguyen, JH Taube, SA Stratton, MH Feuerman, and MC Barton. J Biol Chem 280:39152-39160. WB: p73a and p73b transfected mouse hepatoma (Hepa) cells (Figs 1, 2C and 4A0, adult mouse liver (Fig 4A) and HeLa cells (Fig 4A).  The IMG-246 p73 antibody is validated by p73a and p73a transfected cells (Figs 1 and 2C) in this citation.  
10. Acetylcholinesterase-R increases germ cell apoptosis but enhances sperm motility. Mor I, E Sklan, E Podoly, M Pick, M Kirschner, L Yogev, S Itach, L Schreiber, B Geyer, T Mor, D Grisaru. Journal of Cellular and Molecular Medicine doi: 10.1111/j.1582-4934.2008.00231.x (2008). Imgenex products cited [WB (testicular tissue from male transgenic (TGR) mice)]:
1. IMG-246 (TAp73) Fig. 3D
2. IMG-313 (ΔNp73) Fig. 3D
Note: IMG-246 and IMG-314 detected p73 forms  in whole cell lysate as well as p73 forms that co-immunoprecipitated with RACK1, Fig  3D .
11. Delta TAp73 upregulation correlates with poor prognosis in human tumors: putative in vivo network involving p73 isoforms, p53 and E2F-1. Dominguez G, JM Garcia, C Pena, J Silva, V Garcia, L Martinez, C Maximiano, ME Gomez, JA Rivera, C Garcia-Andrade and F Bonilla. J Clinical Oncology 24:1-11 (2006). Imgenex antibodies cited  [IHC (F) in human colon and breast tumors], Fig 2:
1. p73 (IMG-313A)
2. p73 (IMG-246)
12. Apoptotic function of human PMS₂ compromised by the nonsynonymous single-nucleotide polymorphic varant R₂₀Q. Marinovic-Terzic I, A Yoshioka-Yamashita, H Shimodaira, E Avdievich, I Hunton, R Kolodner, W Edelmann, J Wang. PNAS 105: 13993-13998 (2008). WB (HEK 293T cells), Fig. 2A.
13. Targeting MEK/MAPK signal transduction module potentiates ATO-induced apoptosis in multiple myeloma cells through multiple signaling pathways. Lungli P, N Giuliani, L Mazzera, G Lombardi, M Ricca, A Corradi, A Cantoni, L Salbatore, R Riccioni, A Constanzo, U Testa, M Levrero, V Rizzoli, A Bonati. Blood 112: 2450-2462. Imgenex antibodies cited:
1. p73 (IMG-246): WB (human myeloma cell lines (HMCLs) XG-6 and XG-1), Fig. 4Ci.
2. p73 (deltaNp73) [IMG-313A]: WB (HMCLs), Fig. 4Ai.
3. DcR2 (IMG-121): WB (HMCLs), Fig. 5A. 
14. 1α, 25-Dihydroxyvitamin D₃ potentiates cisplatin antitumor activity by p73 induction in a sqamous cell carcinoma model. Ma Y, W Yu, P Hershberger, G Flynn, R Kong, D Trump, C Johnson. Molecular Cancer Therapeutics 7: 3047-3055 (2008). WB (Mouse SCC cells), Fig. 5A,C.
15. STI571 prevents apoptosis, tau phosphorylation and behavioural impairments induced by Alzheimer's B-amyloid deposits. Cancino G, E Toledo, N Leal, D Hernandez, F Yevenes, N Inestrosa, A Alvarez. Brain 131: 2425-2442 (2008).  Imgenex antibodies cited [WB (rat hippocampal cells)]:
1. IMG-246 (p73): Fig. 5A.
2. IMG-313 (ΔNp73): Fig. 5B.
16. DNA mismatch repair-dependent activation of c-Abl/p73α/GADD45α-mediated apoptosis. Li L, J Morales, A Hwang, M Wagner, D Boothman. jbc 283: 21394-21403 (2008). WB (human colon cancer cell lines HCT116), Fig. 1A,C; 6A.
17. Imatinib therapy blocks cerebellar apoptosis and improves neurological symptoms in a mouse model of Niemann-Pick type C disease. Alvarez A, A Klein, J Castro, G Cancino, J Amigo, M Mosquiera, L Vargas, L Yevenes, F Bronfman, S Zanlungo. The FASEB Journal 22: 3617-3627 (2008). IF/ICC (mouse brain tissue), Fig. 1D.
18. TAp73 regulates the spindle assembly checkpoin by modulating BubR_{1 activity. Tomasini R, K Tsuchihara, C Tsuda, S Lau, M Wilhelm, A Ruffini, M Tsao, J Iovanna, A Juriscova, G Melino, T Mak. PNAS 3: 797-802 (2009).}  WB (human brest cancer cell line MDA-MB-213 and human colon cancer cell line SW480), Fig. 2A, 3A.
19. Regulation of p53 by TopBP1, a potential mechanism for p53 inactivation in cancer.  Liu K, N Bellam, H Lin, B Wang, C Stockard, W Grizzle, W Lin. MCB doi:10.1128/MCB.01140-08 (2009). WB(human Saos-2 cells), Fig. 3D.

20. p73 plays a role in erythroid differentiation through GATA1 induction. Marques-Gacia F, N Ferrandiz, R Fernandez-Alonso, L Gonzalez-Cano, M Herreros-Villanueva, M Rosa-Garrido, B Fernandez-Garcia, J P Vaque, M M Marques, M E Alonso, J C Segovia, J Leon, M C Marin. JBC 284: 21139- 21156 (2009). IMGENEX antibodies cited for ChIP in K562 cells (Figs 4C, 6) and fetal liver extracts from mouse embryos (Fig 10):
1. p73 (IMG-246) 
2. p73 [deltaNp73 (IMG-313)]
21. Association of a p73 exon 2 GC/AT polymorphism with colorectal cancer risk and survival in Tunisian patients. Arfaoui AT, LBM Kriaa, OEA El Hadj, MAB Hmida, M Khiari, T Khalfallah, L Gharbi, S Mzabi, S Bouraoui. Virchows Arch DOI 10.1007/s00428-010-0942-4 (2010). IMGENEX antibodies cited for IHC (paraffin), human colon tumors:
 1. p73 mAb, clone 38C674 (IMG-313A)
2. p73 mAb, clone 5B429 (IMG-246)
 
22. Association of a p73 exon 2 GC/AT polymorphism with colorectal cancer risk and survival in Tunisian patients. Arfaoui AT, LBM Kriaa, OEA El Hadj, MAB Hmida, M Khiari, T Khalfallah, L Gharbi, S Mzabi, S Bouraoui. Virchows Arch DOI 10.1007/s00428-010-0942-4 (2010). IMGENEX antibodies cited for IHC (paraffin), human colon tumors:
 1. p73 mAb, clone 38C674 (IMG-313A)
2. p73 mAb, clone 5B429 (IMG-246)