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  • 1 Al-Kharj University Department of Medical Laboratory Sciences, College of Applied Medial Sciences PO Box 422 Al-Kharj 11942 Saudi Arabia
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Apoptosis stimulating proteins of p53 (ASPP-l and ASPP-2) are a novel family of proteins that have been found to co-stimulate p53 activation of Bax (Bcl-2 associated protein X) inducing caspase-mediated apoptosis. Therefore, these proteins may play an important role in regulating apoptosis in normal and neoplastic cells. However, their cellular and tissue distribution has not been documented. The aim of this study was to determine the localization pattern of ASPP-2 in a variety of normal and malignant human tissues, including liver, lung, prostate, small intestine, kidney, ovary, bladder, cervix, breast, stomach, bowel, gallbladder, endometrium, pancreas, spleen and thyroid.The distribution and expression of ASPP-2 was assessed by immunohistochemistry in a range of formalin-fixed, paraffin embedded, benign and malignant human tissues, using a mouse monoclonal antibody against ASPP-2.The results showed a variable pattern of positivity of ASPP-2 within the tissues studied. ASPP-2 expression was localized in the cytoplasmic paranuclear granules in the epithelial cells of most of the organs we studied. The pattern of staining intensity of ASPP-2 correlated to the maturation state in benign tissue and to the differentiation state in the context of bladder cancer.This study indicates that ASPP-2 has a specific distribution pattern within tissues and cells in a way that appears to be related to differentiation. However, the patterns are neither simplistic nor straightforward and will require further investigation in order to appreciate fully their physiological/pathological significance.

  • Campo, M. L.: Apoptosis. In Salido, G. M., Rosado, J. A. (eds): Apoptosis: Involvement of oxidative stress and intracellular Ca2+ homeostasis. Springer, 2009. DOI 10.1007/978-1-4020-9873-4

  • Wolff, S., Erster, S., Palacios, G., Moll, U. M.: p53’s mitochondrial translocation and MOMP action is independent of Puma and Bax and severely disrupts mitochondrial membrane integrity. Cell Res. 18, 733–744 (2008).

    Moll U. M. , 'p53’s mitochondrial translocation and MOMP action is independent of Puma and Bax and severely disrupts mitochondrial membrane integrity ' (2008 ) 18 Cell Res. : 733 -744.

    • Search Google Scholar
  • Green, D. R., Kroemer, G.: Cytoplasmic functions of the tumor suppressor p53. Nature 458, 1127–1130 (2009).

    Kroemer G. , 'Cytoplasmic functions of the tumor suppressor p53 ' (2009 ) 458 Nature : 1127 -1130.

    • Search Google Scholar
  • Vaseva, A. V., Moll, U. M.: The mitochondrial p53 pathway. Biochim. Biophys. Acta 1787, 414–420 (2009).

    Moll U. M. , 'The mitochondrial p53 pathway ' (2009 ) 1787 Biochim. Biophys. Acta : 414 -420.

  • Speidel, D.: Transcription-independent p53 apoptosis: An alternative route to death (Review). Trends in Cell Biology 20, 14–24 (2010).

    Speidel D. , 'Transcription-independent p53 apoptosis: An alternative route to death (Review) ' (2010 ) 20 Trends in Cell Biology : 14 -24.

    • Search Google Scholar
  • Slee, E. A., Lu, X.: The ASPP family: Deciding between life and death after DNA damage. Toxicology Letters 139, 81–87 (2003).

    Lu X. , 'The ASPP family: Deciding between life and death after DNA damage ' (2003 ) 139 Toxicology Letters : 81 -87.

    • Search Google Scholar
  • Katz, C., Benyamini, H., Rotem, S., Lebendiker, M., Danieli, T., Iosub, A., Refaely, H., Dines, M., Bronner, V., Bravman, T., Shalev, D. E., Rudiger, S., Friedler, A.: Molecular basis of the interaction between the antiapoptotic Bcl-2 family proteins and the proapoptotic protein ASPP2. PNAS USA 105, 12277–12282 (2008).

    Friedler A. , 'Molecular basis of the interaction between the antiapoptotic Bcl-2 family proteins and the proapoptotic protein ASPP2 ' (2008 ) 105 PNAS USA : 12277 -12282.

    • Search Google Scholar
  • Kampa, K. M., Acoba, J. D., Chen, D., Gay, J., Lee, H., Beemer, K., Padiernos, E., Boonmark, N., Zhu, Z., Fan, A. C., Bailey, A. S., Fleming, W. H., Corless, C., Felsher, D. W., Naumovski, L., Lopez, C. D.: Apoptosis-stimulating protein of p53 (ASPP2) heterozygous mice are tumor-prone and have attenuated cellular damage-response thresholds. PNAS USA 106, 4390–4395 (2009).

    Lopez C. D. , 'Apoptosis-stimulating protein of p53 (ASPP2) heterozygous mice are tumor-prone and have attenuated cellular damage-response thresholds ' (2009 ) 106 PNAS USA : 4390 -4395.

    • Search Google Scholar
  • Samuels-Lev, Y., O’Connor, D. J., Bergamaschi, D., Trigiante, G., Hsieh, J. K., Zhong, S. et al.: ASPP proteins specifically stimulate the apoptotic function of p53. Mol. Cell 8, 781–794 (2001).

    Zhong S. , 'ASPP proteins specifically stimulate the apoptotic function of p53 ' (2001 ) 8 Mol. Cell : 781 -794.

    • Search Google Scholar
  • Park, S. W., An, C. H., Kim, S. S., Yoo, N. J., Lee, S. H.: Mutational Analysis of ASPP1 and ASPP2 Genes, a p53-related Gene, in Gastric and Cololorectal Cancers with Microsatellite Instability. Gut. Liver 4(2), 292–293 (2010 Jun). Epub 2010 Jun 16.

    Lee S. H. , 'Mutational Analysis of ASPP1 and ASPP2 Genes, a p53-related Gene, in Gastric and Cololorectal Cancers with Microsatellite Instability ' (2010 ) 4 Gut. Liver : 292 -293.

    • Search Google Scholar
  • Zhao, J., Wu, G., Bu, F., Lu, B., Liang, A., Cao, L., Tong, X., Lu, X., Wu, M., Guo, Y.: Epigenetic silence of ankyrin-repeat-containing, SH3-domain-containing, and prolinerichregion-containing protein 1 (ASPP1) and ASPP2 genes promotes tumor growth in hepatitis B virus-positive hepatocellular carcinoma. Hepatology 51(1), 142–153 (2010).

    Guo Y. , 'Epigenetic silence of ankyrin-repeat-containing, SH3-domain-containing, and prolinerichregion-containing protein 1 (ASPP1) and ASPP2 genes promotes tumor growth in hepatitis B virus-positive hepatocellular carcinoma ' (2010 ) 51 Hepatology : 142 -153.

    • Search Google Scholar
  • Uhlmann-Schiffler, H., Kiermayer, S., Stahl, H.: The DEAD box protein Ddx42p modulates the function of ASPP2, a stimulator of apoptosis. Oncogene 28(20), 2065–2073 (2009 May 21). Epub 2009 Apr 20.

    Stahl H. , 'The DEAD box protein Ddx42p modulates the function of ASPP2, a stimulator of apoptosis ' (2009 ) 28 Oncogene : 2065 -2073.

    • Search Google Scholar
  • Sottocornola, R., Royer, C., Vives, V., Tordella, L., Zhong, S., Wang, Y., Ratnayaka, I., Shipman, M., Cheung, A., Gaston-Massuet, C., Ferretti, P., Molnár, Z., Lu, X.: ASPP2 binds Par-3 and controls the polarity and proliferation of neural progenitors during CNS development. Dev. Cell. 19(1), 126–137 (2010 Jul 20). Epub 2010 Jul 8.

    Lu X. , 'ASPP2 binds Par-3 and controls the polarity and proliferation of neural progenitors during CNS development ' (2010 ) 19 Dev. Cell. : 126 -137.

    • Search Google Scholar
  • Cong, W., Hirose, T., Harita, Y., Yamashita, A., Mizuno, K., Hirano, H., Ohno, S.: ASPP2 regulates epithelial cell polarity through the PAR complex. Curr. Biol. 20(15), 1408–1414 (2010 Aug 10). Epub 2010 Jul 8.

    Ohno S. , 'ASPP2 regulates epithelial cell polarity through the PAR complex ' (2010 ) 20 Curr. Biol. : 1408 -1414.

    • Search Google Scholar
  • Hsu, S. M., Raine, L., Fanger, H.: Use of avidinbiotin-peroxidase complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabeled antibody(PAP) procedures. J. Histochem. Cytochem. 29, 577–580 (1981).

    Fanger H. , 'Use of avidinbiotin-peroxidase complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabeled antibody(PAP) procedures ' (1981 ) 29 J. Histochem. Cytochem. : 577 -580.

    • Search Google Scholar
  • Bergamaschi, D., Samuels, Y., Jin, B., Duraisingham, S., Crook, T., Lu, X.: ASPP1 and ASPP2: common activators of p53 family members. Mol. Cell Biol. 24, 1341–1350 (2004).

    Lu X. , 'ASPP1 and ASPP2: common activators of p53 family members ' (2004 ) 24 Mol. Cell Biol. : 1341 -1350.

    • Search Google Scholar
  • Zhao, J., Wu, G., Bu, F., Lu, B., Liang, A., Cao, L., Tong, X., Lu, X., Wu, M., Guo, Y.: Epigenetic silence of ankyrin-repeat-containing, SH3-domain-containing, and prolinerich-region-containing Protein 1 (ASPP-1) and ASPP-2 genes promotes tumor growth in hepatitis B virus-positive hepatocellular carcinoma. Hepatology 51, 142–153 (2010).

    Guo Y. , 'Epigenetic silence of ankyrin-repeat-containing, SH3-domain-containing, and prolinerich-region-containing Protein 1 (ASPP-1) and ASPP-2 genes promotes tumor growth in hepatitis B virus-positive hepatocellular carcinoma ' (2010 ) 51 Hepatology : 142 -153.

    • Search Google Scholar
  • Trigiante, G., Lu, X.: ASPP and cancer. Nat. Rev. Cancer 6, 217–226 (2006).

    Lu X. , 'ASPP and cancer ' (2006 ) 6 Nat. Rev. Cancer : 217 -226.

  • Sullivan, A., Lu, X.: ASPP: A new family of oncogenes and tumor suppressor genes. Br. J. Cancer 96, 196–200 (2007).

    Lu X. , 'ASPP: A new family of oncogenes and tumor suppressor genes ' (2007 ) 96 Br. J. Cancer : 196 -200.

    • Search Google Scholar
  • Kampa, K. M., Bonin, M., Lopez, C. D.: New insights into the expanding complexity of the tumor suppressor ASPP2. Cell Cycle 8, 2871–2876 (2009).

    Lopez C. D. , 'New insights into the expanding complexity of the tumor suppressor ASPP2 ' (2009 ) 8 Cell Cycle : 2871 -2876.

    • Search Google Scholar
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