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 p73 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. The epitope is thought to lie around the center of the molecule. It reacts with alpha, beta, gamma and delta isoforms of mouse and human p73 as well as the dominant negative p73 (Costanzo, et al, 2002). Because of its reactivity pattern it may be regarded as anti-pan p73. The antibody does not cross react with p53.

Application Notes
1. The clone has also been referred to as 1288 in the literature.
2. Endogenous expression of p73 has been detected in a variety of cell types; please refer to Product Citations for details regarding culture and treatment conditions.
3. Immunoprecipitation details can be found in Sayan et al (2005).
4. IMG-259A has been shown to recongize all the known alternative splicing variants of human and mouse p73 (Costanzo et al, 2002).  
5. 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. 

Endogenous expression of p73 has been detected in a variety of cell types; please refer to Product Citations for details regarding culture and treatment conditions.

Immunoprecipitation details can be found in Sayan et al (2005).

6. 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
1. 20101 [Goat Anti-Mouse Ig HRP Conjugate ]
2. IMG-5019A-1 [Monoclonal Antibody to GAPDH - Loading Control]
3. IMG-5019A-2 [Monoclonal Antibody to GAPDH - Loading Control]

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, CostanzO 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. Treatment with arsenic trioxide (ATO) and MEK1 inhibitor activates the p73-p53AIP1 apoptotic pathway in leukemia cells. Lunghi P, A Costanzo, M Levrero, and A Bonati. Blood, 104: 519-525 (2004). IMGENEX antibodies cited: 1. p73 (IMG-259) [WB, Fig.1 and Fig.2 (NB4 and K562 cell lines)].
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 and J Y. J. Wang. JBC Papers in Press. Published on April 25, 2003 as Manuscript M301962200. IMGENEX antibodies cited: 1. p73 (IMG-259) [WB, Fig.1A (normal thyroid epithelial cells and anaplastic thyroid cells), Fig.1B (follicular (FRO and WRO), papillary (CA300 and CA301) and anaplastic (KAK, C543, and ARO) thyroid cancer cell lines), and Fig.6 (AblNukFKBP-expressing ARO and KAK cells)]. [IP, Fig.1D (human anaplastic thyroid tumors)].
3. p73 is regulated by phosphorylation at the G2/M transition. Marcella Fulco Antonio Costanzo, Paola Merlo, Rosamaria Mangiacasale, Sabrina Strano, Giovanni Blandino,Clara Balsano, Patrizia Lavia and Massimo Levrero et al.,. JBC Papers in Press. Published on August 13, 2003 as Manuscript M304921200. IMGENEX antibodies cited: 1. p73 (IMG-259) [WB, Fig 1ABC, Fig 2A, Fig 3AC, Fig 6A (Hct116 cells) ] , [WB, Fig 4B (transfected p21 U2OS cells) ], [IF/ICC, Fig 5AB (MCF7 and H1299 cells) ].
4. DNA Damage-Dependent Acetylation of p73 Dictates the Selective Activation of Apoptotic Target Genes.  Antonio Costanzo, Paola Merlo, Natalia Pediconi1, Marcella Fulco, Vittorio Sartorelli, Philip A. Cole, Giulia Fontemaggi, Maurizio Fanciulli, Louis Schiltz, Giovanni Blandino, Clara Balsano and Massimo Levrero. Molecular Cell 9: 175-186 (2002). IMGENEX antibodies cited: 1. p73 (IMG-259A) [WB, Fig.1 (HCT116-3 cells)].
5. Exclusion of c-Abl from the nucleus restrains the p73 tumor suppression function. Veronica Vella, Jiangyu Zhu, Francesco Frasca, Chun-Ying Li, Paolo Vigneri, Riccardo Vigneri and Jean Y. J. Wang. J. Biol. Chem. 278: 25151-25157 (2003).
6. p73 is regulated by phosphorylation at the G2/M transition. Marcella Fulco, Antonio Costanzo, Paola Merlo, Rosamaria Mangiacasale, Sabrina Strano, Giovanni Blandino,Clara Balsano, Patrizia Lavia and Massimo Levrero. J. Biol. Chem., Vol. 278, Issue 49, 49196-49202(2003).
7. Adenosine deaminase, a key enzyme in DNA precursors control, is a new p73 target. Apollonia Tullo, Giuseppe Mastropasqua, Jean Christophe Bourdon, Paola Centonze, Monica Gostissa, Antonio Costanzo, Massimo Levrero, Giannino Del Sal, Cecilia Saccone, Elisabetta Sbisà. Oncogene 22, 8738-8748 (2003).
8. The p73 Gene Is an Anti-Tumoral Target of the RARb/g-Selective Retinoid Tazarotene. Marina Papoutsaki, Mauro Lanza, Barbara Marinari, Steven Nistico, Francesca Moretti, Massimo Levrero, Sergio Chimenti and Antonio Costanzo. J Invest Dermatol 123:1162 –1168 (2004).
9. A role of p73 in mitotic exit. Paola Merlo, Marcella Fulco, Antonio Costanzo, Rosamaria Mangiacasale, Sabrina Strano, Giovanni Blandino, Yoichi Taya, Patrizia Lavia, and Massimo Levrero. J. Biol. Chem., Jun 2005; 10.1074/jbc.M500635200.
10. Melanocyte and Keratinocyte Carcinogenesis: p53 Family Protein Activities and Intersecting mRNA Expression Profiles. Molly Kulesz-Martin, James Lagowski, Suzanne Fei, Carl Pelz, Rosalie Sears, Marianne Broome Powell, Ruth Halaban and Jodi Johnson. The Journal of Investigative Dermatology Symposium Proceedings. Volume 0 Issue 0  - July 2005. doi:10.1111/j.1087-0024.2005.200405.x 
11. TP53INP1 is a novel p73 target gene that induces cell cycle arrest and cell death by modulating p73 transcriptional activity. Richard Tomasini, Mylène Seux, Jonathan Nowak, Caroline Bontemps, Alice Carrier, Jean-Charles Dagorn, Marie-Josèphe Pébusque, Juan L Iovanna and Nelson J Dusetti. Oncogene advance online publication 25 July 2005; doi: 10.1038/sj.onc.1208951

12. Skin human papillomavirus type 38 alters p53 functions by accumulation of Np73. Rosita Accardi, Wen Dong, Anouk Smet, Rutao Cui, Agnes Hautefeuille, Anne-Sophie Gabet, Bakary S Sylla, Lutz Gissmann, Pierre Hainaut & Massimo Tommasino. EMBO reports AOP doi:10.1038/sj.embor.7400615, Published online: 6 January 2006. IMGENEX antibodies cited: 1. p73 (IMG-259A) [WB, Fig.3B and Fig.5B (HPV38 keratinocytes)]. [ChIP, Fig.5A (HPV38 keratinocytes)]. [IF/ICC, Fig.6C (keratinocytes of HPV38 E6/E7 transgenic mice)].
13. MEK1 inhibition sensitizes primary acute myelogenous leukemia to arsenic trioxide-induced apoptosis. Paolo Lunghi, Antonio Costanzo, Luigi Salvatore, Nelida Noguera, Laura Mazzera, Antonio Tabilio, Francesco Lo-Coco, Massimo Levrero, and Antonio Bonati. Blood, Feb 2006; 10.1182/blood-2005-07-2829.    
14. DNp73á protects myogenic cells from apoptosis. L Belloni, F Moretti, P Merlo, A Damalas, A Costanzo, G Blandino, M Levrero. Oncogene 25, 3606-3612 (2006).
15. 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).
16. 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).   
17. 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.